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2,297 results on '"Cantley, Lewis C."'

1. The intrinsic substrate specificity of the human tyrosine kinome

Author

Yaron-Barir, Tomer M., Joughin, Brian A., Huntsman, Emily M., Kerelsky, Alexander, Cizin, Daniel M., Cohen, Benjamin M., Regev, Amit, Song, Junho, Vasan, Neil, Lin, Ting-Yu, Orozco, Jose M., Schoenherr, Christina, Sagum, Cari, Bedford, Mark T., Wynn, R. Max, Tso, Shih-Chia, Chuang, David T., Li, Lei, Li, Shawn S.-C., Creixell, Pau, Krismer, Konstantin, Takegami, Mina, Lee, Harin, Zhang, Bin, Lu, Jingyi, Cossentino, Ian, Landry, Sean D., Uduman, Mohamed, Blenis, John, Elemento, Olivier, Frame, Margaret C., Hornbeck, Peter V., Cantley, Lewis C., Turk, Benjamin E., Yaffe, Michael B., and Johnson, Jared L.

Published
2024
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2. Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation

Author

Rogava, Meri, Aprati, Tyler J., Chi, Wei-Yu, Melms, Johannes C., Hug, Clemens, Davis, Stephanie H., Earlie, Ethan M., Chung, Charlie, Deshmukh, Sachin K., Wu, Sharon, Sledge, George, Tang, Stephen, Ho, Patricia, Amin, Amit Dipak, Caprio, Lindsay, Gurjao, Carino, Tagore, Somnath, Ngo, Bryan, Lee, Michael J., Zanetti, Giorgia, Wang, Yiping, Chen, Sean, Ge, William, Melo, Luiza Martins Nascentes, Allies, Gabriele, Rösler, Jonas, Gibney, Goeffrey T., Schmitz, Oliver J., Sykes, Megan, Creusot, Rémi J., Tüting, Thomas, Schadendorf, Dirk, Röcken, Martin, Eigentler, Thomas K., Molotkov, Andrei, Mintz, Akiva, Bakhoum, Samuel F., Beyaz, Semir, Cantley, Lewis C., Sorger, Peter K., Meckelmann, Sven W., Tasdogan, Alpaslan, Liu, David, Laughney, Ashley M., and Izar, Benjamin

Published
2024
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3. Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication

Author

Yaron, Tomer M, Heaton, Brook E, Levy, Tyler M, Johnson, Jared L, Jordan, Tristan X, Cohen, Benjamin M, Kerelsky, Alexander, Lin, Ting-Yu, Liberatore, Katarina M, Bulaon, Danielle K, Van Nest, Samantha J, Koundouros, Nikos, Kastenhuber, Edward R, Mercadante, Marisa N, Shobana-Ganesh, Kripa, He, Long, Schwartz, Robert E, Chen, Shuibing, Weinstein, Harel, Elemento, Olivier, Piskounova, Elena, Nilsson-Payant, Benjamin E, Lee, Gina, Trimarco, Joseph D, Burke, Kaitlyn N, Hamele, Cait E, Chaparian, Ryan R, Harding, Alfred T, Tata, Aleksandra, Zhu, Xinyu, Tata, Purushothama Rao, Smith, Clare M, Possemato, Anthony P, Tkachev, Sasha L, Hornbeck, Peter V, Beausoleil, Sean A, Anand, Shankara K, Aguet, François, Getz, Gad, Davidson, Andrew D, Heesom, Kate, Kavanagh-Williamson, Maia, Matthews, David A, tenOever, Benjamin R, Cantley, Lewis C, Blenis, John, and Heaton, Nicholas S

Subjects
Pneumonia & Influenza, Prevention, Immunization, Biotechnology, Vaccine Related, Lung, Emerging Infectious Diseases, Infectious Diseases, Infection, Good Health and Well Being, Animals, Humans, SARS-CoV-2, Phosphorylation, COVID-19, Glycogen Synthase Kinase 3, Virus Replication, Nucleocapsid Proteins, Nucleocapsid, Serine, Threonine, Mammals, Protein Serine-Threonine Kinases, Biochemistry and Cell Biology
Abstract

Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.

Published
2022

4. Author Correction: Identification of SARS-CoV-2 inhibitors using lung and colonic organoids

Author

Han, Yuling, Duan, Xiaohua, Yang, Liuliu, Nilsson-Payant, Benjamin E., Wang, Pengfei, Duan, Fuyu, Tang, Xuming, Yaron, Tomer M., Zhang, Tuo, Uhl, Skyler, Bram, Yaron, Richardson, Chanel, Zhu, Jiajun, Zhao, Zeping, Redmond, David, Houghton, Sean, Nguyen, Duc-Huy T., Xu, Dong, Wang, Xing, Jessurun, Jose, Borczuk, Alain, Huang, Yaoxing, Johnson, Jared L., Liu, Yuru, Xiang, Jenny, Wang, Hui, Cantley, Lewis C., tenOever, Benjamin R., Ho, David D., Pan, Fong Cheng, Evans, Todd, Chen, Huanhuan Joyce, Schwartz, Robert E., and Chen, Shuibing

Published
2024
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6. Multi-scale signaling and tumor evolution in high-grade gliomas

Author

Liu, Jingxian, Cao, Song, Imbach, Kathleen J., Gritsenko, Marina A., Lih, Tung-Shing M., Kyle, Jennifer E., Yaron-Barir, Tomer M., Binder, Zev A., Li, Yize, Strunilin, Ilya, Wang, Yi-Ting, Tsai, Chia-Feng, Ma, Weiping, Chen, Lijun, Clark, Natalie M., Shinkle, Andrew, Naser Al Deen, Nataly, Caravan, Wagma, Houston, Andrew, Simin, Faria Anjum, Wyczalkowski, Matthew A., Wang, Liang-Bo, Storrs, Erik, Chen, Siqi, Illindala, Ritvik, Li, Yuping D., Jayasinghe, Reyka G., Rykunov, Dmitry, Cottingham, Sandra L., Chu, Rosalie K., Weitz, Karl K., Moore, Ronald J., Sagendorf, Tyler, Petyuk, Vladislav A., Nestor, Michael, Bramer, Lisa M., Stratton, Kelly G., Schepmoes, Athena A., Couvillion, Sneha P., Eder, Josie, Kim, Young-Mo, Gao, Yuqian, Fillmore, Thomas L., Zhao, Rui, Monroe, Matthew E., Southard-Smith, Austin N., Li, Yang E., Jui-Hsien Lu, Rita, Johnson, Jared L., Wiznerowicz, Maciej, Hostetter, Galen, Newton, Chelsea J., Ketchum, Karen A., Thangudu, Ratna R., Barnholtz-Sloan, Jill S., Wang, Pei, Fenyö, David, An, Eunkyung, Thiagarajan, Mathangi, Robles, Ana I., Mani, D.R., Smith, Richard D., Porta-Pardo, Eduard, Cantley, Lewis C., Iavarone, Antonio, Chen, Feng, Mesri, Mehdi, Nasrallah, MacLean P., Zhang, Hui, Resnick, Adam C., Chheda, Milan G., Rodland, Karin D., Liu, Tao, and Ding, Li

Published
2024
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8. Depletion of creatine phosphagen energetics with a covalent creatine kinase inhibitor

Author

Darabedian, Narek, Ji, Wenzhi, Fan, Mengyang, Lin, Shan, Seo, Hyuk-Soo, Vinogradova, Ekaterina V., Yaron, Tomer M., Mills, Evanna L., Xiao, Haopeng, Senkane, Kristine, Huntsman, Emily M., Johnson, Jared L., Che, Jianwei, Cantley, Lewis C., Cravatt, Benjamin F., Dhe-Paganon, Sirano, Stegmaier, Kimberly, Zhang, Tinghu, Gray, Nathanael S., and Chouchani, Edward T.

Published
2023
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10. Pan-cancer proteogenomics characterization of tumor immunity

Author

Abelin, Jennifer, Aguet, François, Akiyama, Yo, An, Eunkyung, Anand, Shankara, Anurag, Meenakshi, Babur, Özgün, Bavarva, Jasmin, Birger, Chet, Birrer, Michael J., Cao, Song, Carr, Steven A., Chan, Daniel W., Chinnaiyan, Arul M., Cho, Hanbyul, Clauser, Karl, Colaprico, Antonio, Zhou, Daniel Cui, da Veiga Leprevost, Felipe, Day, Corbin, Dhanasekaran, Saravana M., Ding, Li, Domagalski, Marcin J., Dou, Yongchao, Druker, Brian J., Edwards, Nathan, Ellis, Matthew J., Foltz, Steven M., Francis, Alicia, Geffen, Yifat, Getz, Gad, Heiman, David I., Hong, Runyu, Hu, Yingwei, Huang, Chen, Jaehnig, Eric J., Jewell, Scott D., Ji, Jiayi, Jiang, Wen, Katsnelson, Lizabeth, Ketchum, Karen A., Kolodziejczak, Iga, Krug, Karsten, Kumar-Sinha, Chandan, Lei, Jonathan T., Liang, Wen-Wei, Liao, Yuxing, Lindgren, Caleb M., Liu, Tao, Liu, Wenke, McDermott, Jason, McKerrow, Wilson, Mesri, Mehdi, Mumphrey, Michael Brodie, Newton, Chelsea J., Oldroyd, Robert, Payne, Samuel H., Pugliese, Pietro, Rodland, Karin D., Rodrigues, Fernanda Martins, Ruggles, Kelly V., Savage, Sara R., Schadt, Eric E., Schnaubelt, Michael, Schraink, Tobias, Schürer, Stephan, Shi, Zhiao, Smith, Richard D., Song, Feng, Song, Yizhe, Stathias, Vasileios, Storrs, Erik P., Tan, Jimin, Terekhanova, Nadezhda V., Thangudu, Ratna R., Thiagarajan, Mathangi, Wang, Liang-Bo, Wen, Bo, Wu, Yige, Wyczalkowski, Matthew A., Yao, Lijun, Li, Qing Kay, Zhang, Hui, Zhang, Qing, Zhang, Xu, Zhang, Zhen, Petralia, Francesca, Ma, Weiping, Yaron, Tomer M., Caruso, Francesca Pia, Tignor, Nicole, Wang, Joshua M., Charytonowicz, Daniel, Johnson, Jared L., Huntsman, Emily M., Marino, Giacomo B., Calinawan, Anna, Evangelista, John Erol, Selvan, Myvizhi Esai, Chowdhury, Shrabanti, Rykunov, Dmitry, Krek, Azra, Song, Xiaoyu, Turhan, Berk, Christianson, Karen E., Lewis, David A., Deng, Eden Z., Clarke, Daniel J.B., Whiteaker, Jeffrey R., Kennedy, Jacob J., Zhao, Lei, Segura, Rossana Lazcano, Batra, Harsh, Raso, Maria Gabriela, Parra, Edwin Roger, Soundararajan, Rama, Tang, Ximing, Li, Yize, Yi, Xinpei, Satpathy, Shankha, Wang, Ying, Wiznerowicz, Maciej, González-Robles, Tania J., Iavarone, Antonio, Gosline, Sara J.C., Reva, Boris, Robles, Ana I., Nesvizhskii, Alexey I., Mani, D.R., Gillette, Michael A., Klein, Robert J., Cieslik, Marcin, Zhang, Bing, Paulovich, Amanda G., Sebra, Robert, Gümüş, Zeynep H., Hostetter, Galen, Fenyö, David, Omenn, Gilbert S., Cantley, Lewis C., Ma'ayan, Avi, Lazar, Alexander J., Ceccarelli, Michele, and Wang, Pei

Published
2024
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11. The carbohydrate-insulin model: a physiological perspective on the obesity pandemic

Author

Ludwig, David S, Aronne, Louis J, Astrup, Arne, de Cabo, Rafael, Cantley, Lewis C, Friedman, Mark I, Heymsfield, Steven B, Johnson, James D, King, Janet C, Krauss, Ronald M, Lieberman, Daniel E, Taubes, Gary, Volek, Jeff S, Westman, Eric C, Willett, Walter C, Yancy, William S, and Ebbeling, Cara B

Subjects
Prevention, Obesity, Nutrition, Cancer, Cardiovascular, Oral and gastrointestinal, Metabolic and endocrine, Stroke, Affordable and Clean Energy, Carbohydrates, Dietary Carbohydrates, Dietary Fats, Energy Intake, Energy Metabolism, Humans, Insulin, Pandemics, obesity, weight loss, dietary carbohydrate, energy balance, macronutrients, endocrinology, insulin, glucagon, incretins, scholarly discourse, Engineering, Medical and Health Sciences, Nutrition & Dietetics
Abstract

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body-resulting from the hormonal responses to a high-glycemic-load diet-drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.

Published
2021

12. An atlas of substrate specificities for the human serine/threonine kinome

Author

Johnson, Jared L., Yaron, Tomer M., Huntsman, Emily M., Kerelsky, Alexander, Song, Junho, Regev, Amit, Lin, Ting-Yu, Liberatore, Katarina, Cizin, Daniel M., Cohen, Benjamin M., Vasan, Neil, Ma, Yilun, Krismer, Konstantin, Robles, Jaylissa Torres, van de Kooij, Bert, van Vlimmeren, Anne E., Andrée-Busch, Nicole, Käufer, Norbert F., Dorovkov, Maxim V., Ryazanov, Alexey G., Takagi, Yuichiro, Kastenhuber, Edward R., Goncalves, Marcus D., Hopkins, Benjamin D., Elemento, Olivier, Taatjes, Dylan J., Maucuer, Alexandre, Yamashita, Akio, Degterev, Alexei, Uduman, Mohamed, Lu, Jingyi, Landry, Sean D., Zhang, Bin, Cossentino, Ian, Linding, Rune, Blenis, John, Hornbeck, Peter V., Turk, Benjamin E., Yaffe, Michael B., and Cantley, Lewis C.

Published
2023
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13. Epinephrine inhibits PI3Kα via the Hippo kinases

Author

Lin, Ting-Yu, Ramsamooj, Shakti, Perrier, Tiffany, Liberatore, Katarina, Lantier, Louise, Vasan, Neil, Karukurichi, Kannan, Hwang, Seo-Kyoung, Kesicki, Edward A., Kastenhuber, Edward R., Wiederhold, Thorsten, Yaron, Tomer M., Huntsman, Emily M., Zhu, Mengmeng, Ma, Yilun, Paddock, Marcia N., Zhang, Guoan, Hopkins, Benjamin D., McGuinness, Owen, Schwartz, Robert E., Ersoy, Baran A., Cantley, Lewis C., Johnson, Jared L., and Goncalves, Marcus D.

Published
2023
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14. Deep learning integrates histopathology and proteogenomics at a pan-cancer level

Author

Aguet, François, Akiyama, Yo, Anand, Shankara, Anurag, Meenakshi, Babur, Özgün, Bavarva, Jasmin, Birger, Chet, Birrer, Michael J., Cantley, Lewis C., Cao, Song, Carr, Steven A., Ceccarelli, Michele, Chan, Daniel W., Chinnaiyan, Arul M., Cho, Hanbyul, Chowdhury, Shrabanti, Cieslik, Marcin P., Clauser, Karl R., Colaprico, Antonio, Zhou, Daniel Cui, da Veiga Leprevost, Felipe, Day, Corbin, Dhanasekaran, Saravana M., Domagalski, Marcin J., Dou, Yongchao, Druker, Brian J., Edwards, Nathan, Ellis, Matthew J., Selvan, Myvizhi Esai, Foltz, Steven M., Francis, Alicia, Geffen, Yifat, Getz, Gad, Gonzalez Robles, Tania J., Gosline, Sara J.C., Gümüş, Zeynep H., Heiman, David I., Hiltke, Tara, Hostetter, Galen, Hu, Yingwei, Huang, Chen, Huntsman, Emily, Iavarone, Antonio, Jaehnig, Eric J., Jewell, Scott D., Ji, Jiayi, Jiang, Wen, Johnson, Jared L., Katsnelson, Lizabeth, Ketchum, Karen A., Kolodziejczak, Iga, Krug, Karsten, Kumar-Sinha, Chandan, Lei, Jonathan T., Liang, Wen-Wei, Liao, Yuxing, Lindgren, Caleb M., Liu, Tao, Ma, Weiping, Rodrigues, Fernanda Martins, McKerrow, Wilson, Mesri, Mehdi, Nesvizhskii, Alexey I., Newton, Chelsea J., Oldroyd, Robert, Paulovich, Amanda G., Payne, Samuel H., Petralia, Francesca, Pugliese, Pietro, Reva, Boris, Rykunov, Dmitry, Satpathy, Shankha, Savage, Sara R., Schadt, Eric E., Schnaubelt, Michael, Schürer, Stephan, Shi, Zhiao, Smith, Richard D., Song, Xiaoyu, Song, Yizhe, Stathias, Vasileios, Storrs, Erik P., Terekhanova, Nadezhda V., Thangudu, Ratna R., Thiagarajan, Mathangi, Tignor, Nicole, Wang, Liang-Bo, Wang, Pei, Wang, Ying, Wen, Bo, Wiznerowicz, Maciej, Wu, Yige, Wyczalkowski, Matthew A., Yao, Lijun, Yaron, Tomer M., Yi, Xinpei, Zhang, Bing, Zhang, Hui, Zhang, Qing, Zhang, Xu, Zhang, Zhen, Wang, Joshua M., Hong, Runyu, Demicco, Elizabeth G., Tan, Jimin, Lazcano, Rossana, Moreira, Andre L., Li, Yize, Calinawan, Anna, Razavian, Narges, Schraink, Tobias, Gillette, Michael A., Omenn, Gilbert S., An, Eunkyung, Rodriguez, Henry, Tsirigos, Aristotelis, Ruggles, Kelly V., Ding, Li, Robles, Ana I., Mani, D.R., Rodland, Karin D., Lazar, Alexander J., Liu, Wenke, and Fenyö, David

Published
2023
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15. Integrative multi-omic cancer profiling reveals DNA methylation patterns associated with therapeutic vulnerability and cell-of-origin

Author

Aguet, François, Akiyama, Yo, An, Eunkyung, Anand, Shankara, Anurag, Meenakshi, Babur, Ozgun, Bavarva, Jasmin, Birger, Chet, Birrer, Michael, Calinawan, Anna, Cantley, Lewis C., Cao, Song, Carr, Steve, Ceccarelli, Michele, Chan, Daniel, Chinnaiyan, Arul, Cho, Hanbyul, Chowdhury, Shrabanti, Cieslik, Marcin, Clauser, Karl, Colaprico, Antonio, Zhou, Daniel Cui, da Veiga Leprevost, Felipe, Day, Corbin, Dhanasekaran, Mohan, Domagalski, Marcin, Dou, Yongchao, Druker, Brian, Edwards, Nathan, Ellis, Matthew, Selvan, Myvizhi Esai, Francis, Alicia, Getz, Gad, Gillette, Michael A., Robles, Tania Gonzalez, Gosline, Sara, Gümüş, Zeynep, Heiman, David, Hiltke, Tara, Hong, Runyu, Hostetter, Galen, Hu, Yingwei, Huang, Chen, Huntsman, Emily, Iavarone, Antonio, Jaehnig, Eric, Jewel, Scott, Ji, Jiayi, Jiang, Wen, Lee Johnson, Jared, Katsnelson, Lizabeth, Ketchum, Karen, Krug, Karsten, Kumar-Sinha, Chandan, Lei, Jonathan, Liao, Yuxing, Lindgren, Caleb, Liu, Tao, Liu, Wenke, Ma, Weiping, Rodrigues, Fernanda Martins, McKerrow, Wilson, Mesri, Mehdi, Nesvizhskii, Alexey I., Newton, Chelsea, Oldroyd, Robert, Omenn, Gilbert, Paulovich, Amanda, Petralia, Francesca, Pugliese, Pietro, Reva, Boris, Ruggles, Kelly, Rykunov, Dmitry, Satpathy, Shankha, Savage, Sara, Schadt, Eric, Schnaubelt, Michael, Schraink, Tobias, Shi, Zhiao, Smith, Dick, Song, Xiaoyu, Stathias, Vasileios, Storrs, Erik, Tan, Jimin, Terekhanova, Nadezhda, Thangudu, Ratna, Thiagarajan, Mathangi, Tignor, Nicole, Wang, Joshua, Wang, Liang-Bo, Wang, Pei, Wang, Ying (Cindy), Wen, Bo, Wu, Yige, Yao, Lijun, Yaron, Tomer M., Yi, Xinpei, Zhang, Bing, Zhang, Hui, Zhang, Qing, Zhang, Xu, Zhang, Zhen, Chan, Daniel W., Dhanasekaran, Saravana M., Schürer, Stephan, Smith, Richard D., Wyczalkowski, Matthew A., Liang, Wen-Wei, Lu, Rita Jui-Hsien, Jayasinghe, Reyka G., Foltz, Steven M., Porta-Pardo, Eduard, Geffen, Yifat, Wendl, Michael C., Lazcano, Rossana, Kolodziejczak, Iga, Song, Yizhe, Govindan, Akshay, Demicco, Elizabeth G., Li, Xiang, Li, Yize, Sethuraman, Sunantha, Payne, Samuel H., Fenyö, David, Rodriguez, Henry, Wiznerowicz, Maciej, Shen, Hui, Mani, D.R., Rodland, Karin D., Lazar, Alexander J., Robles, Ana I., and Ding, Li

Published
2023
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16. Pan-cancer analysis of post-translational modifications reveals shared patterns of protein regulation

Author

An, Eunkyung, Anurag, Meenakshi, Bavarva, Jasmin, Birrer, Michael J., Babur, Özgün, Cao, Song, Ceccarelli, Michele, Chan, Daniel W., Chinnaiyan, Arul M., Cho, Hanbyul, Chowdhury, Shrabanti, Cieslik, Marcin P., Colaprico, Antonio, Carr, Steven A., da Veiga Leprevost, Felipe, Day, Corbin, Domagalski, Marcin J., Dou, Yongchao, Druker, Brian J., Edwards, Nathan, Ellis, Matthew J., Fenyo, David, Foltz, Steven M., Francis, Alicia, Gonzalez Robles, Tania J., Gosline, Sara J.C., Gümüş, Zeynep H., Hiltke, Tara, Hong, Runyu, Hostetter, Galen, Hu, Yingwei, Huang, Chen, Iavarone, Antonio, Jaehnig, Eric J., Jewel, Scott D., Ji, Jiayi, Jiang, Wen, Katsnelson, Lizabeth, Ketchum, Karen A., Kolodziejczak, Iga, Kumar-Sinha, Chandan, Krug, Karsten, Lei, Jonathan T., Liang, Wen-Wei, Liao, Yuxing, Lindgren, Caleb M., Liu, Tao, Liu, Wenke, Ma, Weiping, McKerrow, Wilson, Mesri, Mehdi, Mani, D.R., Nesvizhskii, Alexey I., Newton, Chelsea, Oldroyd, Robert, Omenn, Gilbert S., Paulovich, Amanda G., Petralia, Francesca, Pugliese, Pietro, Reva, Boris, Rodland, Karin D., Ruggles, Kelly V., Rykunov, Dmitry, Rodrigues, Fernanda Martins, Savage, Sara R., Schadt, Eric E., Schnaubelt, Michael, Schraink, Tobias, Shi, Zhiao, Smith, Richard D., Song, Xiaoyu, Stathias, Vasileios, Storrs, Erik P., Schürer, Stephan, Selvan, Myvizhi Esai, Tan, Jimin, Terekhanova, Nadezhda V., Thangudu, Ratna R., Tignor, Nicole, Thiagarajan, Mathangi, Wang, Joshua M., Wang, Pei, Wang, Ying (Cindy), Wen, Bo, Wiznerowicz, Maciej, Wu, Yige, Wyczalkowski, Matthew A., Yao, Lijun, Yi, Xinpei, Zhang, Bing, Zhang, Hui, Zhang, Xu, Zhang, Zhen, Zhou, Daniel Cui, Geffen, Yifat, Anand, Shankara, Akiyama, Yo, Yaron, Tomer M., Song, Yizhe, Johnson, Jared L., Govindan, Akshay, Li, Yize, Huntsman, Emily, Wang, Liang-Bo, Birger, Chet, Heiman, David I., Zhang, Qing, Miller, Mendy, Maruvka, Yosef E., Haradhvala, Nicholas J., Calinawan, Anna, Belkin, Saveliy, Kerelsky, Alexander, Clauser, Karl R., Satpathy, Shankha, Payne, Samuel H., Gillette, Michael A., Dhanasekaran, Saravana M., Rodriguez, Henry, Robles, Ana I., Lazar, Alexander J., Aguet, François, Cantley, Lewis C., Ding, Li, and Getz, Gad

Published
2023
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17. Pan-cancer proteogenomics connects oncogenic drivers to functional states

Author

An, Eunkyung, Anurag, Meenakshi, Bavarva, Jasmin, Birrer, Michael J., Calinawan, Anna, Ceccarelli, Michele, Chan, Daniel W., Chinnaiyan, Arul M., Cho, Hanbyul, Chowdhury, Shrabanti, Cieslik, Marcin P., da Veiga Leprevost, Felipe, Day, Corbin, Domagalski, Marcin J., Dou, Yongchao, Druker, Brian J., Edwards, Nathan, Ellis, Matthew J., Selvan, Myvizhi Esai, Foltz, Steven M., Francis, Alicia, Gonzalez Robles, Tania J., Gosline, Sara J.C., Gümüş, Zeynep H., Hiltke, Tara, Hong, Runyu, Hostetter, Galen, Hu, Yingwei, Huang, Chen, Huntsman, Emily, Jaehnig, Eric J., Jewel, Scott D., Ji, Jiayi, Jiang, Wen, Katsnelson, Lizabeth, Ketchum, Karen A., Kolodziejczak, Iga, Lei, Jonathan T., Liao, Yuxing, Lindgren, Caleb M., Liu, Tao, Ma, Weiping, McKerrow, Wilson, Nesvizhskii, Alexey I., Newton, Chelsea, Oldroyd, Robert, Omenn, Gilbert S., Paulovich, Amanda G., Petralia, Francesca, Reva, Boris, Rodland, Karin D., Ruggles, Kelly V., Rykunov, Dmitry, Savage, Sara R., Schadt, Eric E., Schnaubelt, Michael, Schraink, Tobias, Shi, Zhiao, Smith, Richard D., Song, Xiaoyu, Tan, Jimin, Thangudu, Ratna R., Tignor, Nicole, Wang, Joshua M., Wang, Pei, Wang, Ying (Cindy), Wen, Bo, Wiznerowicz, Maciej, Yi, Xinpei, Zhang, Bing, Zhang, Hui, Zhang, Xu, Zhang, Zhen, Li, Yize, Porta-Pardo, Eduard, Tokheim, Collin, Bailey, Matthew H., Yaron, Tomer M., Stathias, Vasileios, Geffen, Yifat, Imbach, Kathleen J., Cao, Song, Anand, Shankara, Akiyama, Yo, Liu, Wenke, Wyczalkowski, Matthew A., Song, Yizhe, Storrs, Erik P., Wendl, Michael C., Zhang, Wubing, Sibai, Mustafa, Ruiz-Serra, Victoria, Liang, Wen-Wei, Terekhanova, Nadezhda V., Rodrigues, Fernanda Martins, Clauser, Karl R., Heiman, David I., Zhang, Qing, Aguet, Francois, Calinawan, Anna P., Dhanasekaran, Saravana M., Birger, Chet, Satpathy, Shankha, Zhou, Daniel Cui, Wang, Liang-Bo, Baral, Jessika, Johnson, Jared L., Huntsman, Emily M., Pugliese, Pietro, Colaprico, Antonio, Iavarone, Antonio, Chheda, Milan G., Ricketts, Christopher J., Fenyö, David, Payne, Samuel H., Rodriguez, Henry, Robles, Ana I., Gillette, Michael A., Kumar-Sinha, Chandan, Lazar, Alexander J., Cantley, Lewis C., Getz, Gad, and Ding, Li

Published
2023
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18. Proteogenomic data and resources for pan-cancer analysis

Author

Lazar, Alexander J., Paulovich, Amanda G., Colaprico, Antonio, Iavarone, Antonio, Chinnaiyan, Arul M., Druker, Brian J., Kumar-Sinha, Chandan, Newton, Chelsea J., Huang, Chen, Mani, D.R., Smith, Richard D., Huntsman, Emily, Schadt, Eric E., An, Eunkyung, Petralia, Francesca, Hostetter, Galen, Omenn, Gilbert S., Cho, Hanbyul, Rodriguez, Henry, Zhang, Hui, Kolodziejczak, Iga, Johnson, Jared L., Bavarva, Jasmin, Tan, Jimin, Rodland, Karin D., Clauser, Karl R., Krug, Karsten, Cantley, Lewis C., Wiznerowicz, Maciej, Ellis, Matthew J., Anurag, Meenakshi, Mesri, Mehdi, Gillette, Michael A., Birrer, Michael J., Ceccarelli, Michele, Dhanasekaran, Saravana M., Edwards, Nathan, Tignor, Nicole, Babur, Özgün, Pugliese, Pietro, Gosline, Sara J.C., Jewell, Scott D., Satpathy, Shankha, Chowdhury, Shrabanti, Schürer, Stephan, Carr, Steven A., Liu, Tao, Hiltke, Tara, Yaron, Tomer M., Stathias, Vasileios, Liu, Wenke, Zhang, Xu, Song, Yizhe, Zhang, Zhen, Li, Yize, Dou, Yongchao, Da Veiga Leprevost, Felipe, Geffen, Yifat, Calinawan, Anna P., Aguet, François, Akiyama, Yo, Anand, Shankara, Birger, Chet, Cao, Song, Chaudhary, Rekha, Chilappagari, Padmini, Cieslik, Marcin, Zhou, Daniel Cui, Day, Corbin, Domagalski, Marcin J., Esai Selvan, Myvizhi, Fenyö, David, Foltz, Steven M., Francis, Alicia, Gonzalez-Robles, Tania, Gümüş, Zeynep H., Heiman, David, Holck, Michael, Hong, Runyu, Hu, Yingwei, Jaehnig, Eric J., Ji, Jiayi, Jiang, Wen, Katsnelson, Lizabeth, Ketchum, Karen A., Klein, Robert J., Lei, Jonathan T., Liang, Wen-Wei, Liao, Yuxing, Lindgren, Caleb M., Ma, Weiping, Ma, Lei, MacCoss, Michael J., Martins Rodrigues, Fernanda, McKerrow, Wilson, Nguyen, Ngoc, Oldroyd, Robert, Pilozzi, Alexander, Reva, Boris, Rudnick, Paul, Ruggles, Kelly V., Rykunov, Dmitry, Savage, Sara R., Schnaubelt, Michael, Schraink, Tobias, Shi, Zhiao, Singhal, Deepak, Song, Xiaoyu, Storrs, Erik, Terekhanova, Nadezhda V., Thangudu, Ratna R., Thiagarajan, Mathangi, Wang, Liang-Bo, Wang, Joshua M., Wang, Ying, Wen, Bo, Wu, Yige, Wyczalkowski, Matthew A., Xin, Yi, Yao, Lijun, Yi, Xinpei, Zhang, Qing, Zuhl, Maya, Getz, Gad, Ding, Li, Nesvizhskii, Alexey I., Wang, Pei, Robles, Ana I., Zhang, Bing, and Payne, Samuel H.

Published
2023
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21. PI3K drives the de novo synthesis of coenzyme A from vitamin B5

Author

Dibble, Christian C., Barritt, Samuel A., Perry, Grace E., Lien, Evan C., Geck, Renee C., DuBois-Coyne, Sarah E., Bartee, David, Zengeya, Thomas T., Cohen, Emily B., Yuan, Min, Hopkins, Benjamin D., Meier, Jordan L., Clohessy, John G., Asara, John M., Cantley, Lewis C., and Toker, Alex

Published
2022
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24. Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer

Author

Klomp, Jennifer E., primary, Diehl, J. Nathaniel, additional, Klomp, Jeffrey A., additional, Edwards, A. Cole, additional, Yang, Runying, additional, Morales, Alexis J., additional, Taylor, Khalilah E., additional, Drizyte-Miller, Kristina, additional, Bryant, Kirsten L., additional, Schaefer, Antje, additional, Johnson, Jared L., additional, Huntsman, Emily M., additional, Yaron, Tomer M., additional, Pierobon, Mariaelena, additional, Baldelli, Elisa, additional, Prevatte, Alex W., additional, Barker, Natalie K., additional, Herring, Laura E., additional, Petricoin, Emanuel F., additional, Graves, Lee M., additional, Cantley, Lewis C., additional, Cox, Adrienne D., additional, Der, Channing J., additional, and Stalnecker, Clint A., additional

Published
2024
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25. Malic enzyme 1 knockout has no deleterious phenotype and is favored in the male germline under standard laboratory conditions

Author

Alektiar, Jonathan M., primary, Shan, Mengrou, additional, Radyk, Megan D., additional, Zhang, Li, additional, Halbrook, Christopher J., additional, Lin, Lin, additional, Espinoza, Carlos, additional, Mier, Ivan F., additional, Lavoie, Brooke L., additional, Salvatore, Lucie, additional, Pasca di Magliano, Marina, additional, Cantley, Lewis C., additional, Mueller, Jacob L., additional, and Lyssiotis, Costas A., additional

Published
2024
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26. Genome-wide CRISPR screens in spheroid culture reveal that the tumor suppressor LKB1 inhibits growth via the PIKFYVE lipid kinase

Author

Ferrarone, John R., primary, Thomas, Jerin, additional, Unni, Arun M., additional, Zheng, Yuxiang, additional, Nagiec, Michal J., additional, Gardner, Eric E., additional, Mashadova, Oksana, additional, Li, Kate, additional, Koundouros, Nikos, additional, Montalbano, Antonino, additional, Mustafa, Meer, additional, Cantley, Lewis C., additional, Blenis, John, additional, Sanjana, Neville E., additional, and Varmus, Harold, additional

Published
2024
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29. Mitochondrial One-Carbon Pathway Supports Cytosolic Folate Integrity in Cancer Cells

Author

Zheng, Yuxiang, Lin, Ting-Yu, Lee, Gina, Paddock, Marcia N, Momb, Jessica, Cheng, Zhe, Li, Qian, Fei, Dennis L, Stein, Benjamin D, Ramsamooj, Shivan, Zhang, Guoan, Blenis, John, and Cantley, Lewis C

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Nutrition, Complementary and Integrative Health, Cancer, Carbon, Cytosol, Formates, HCT116 Cells, HeLa Cells, Humans, MCF-7 Cells, Methotrexate, Mitochondria, Mitochondrial Proteins, Neoplasm Proteins, Neoplasms, Tetrahydrofolate Dehydrogenase, Tetrahydrofolates, Hela Cells, folate, formate, metabolism, methotrexate, mitochondria, one-carbon, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Mammalian folate metabolism is comprised of cytosolic and mitochondrial pathways with nearly identical core reactions, yet the functional advantages of such an organization are not well understood. Using genome-editing and biochemical approaches, we find that ablating folate metabolism in the mitochondria of mammalian cell lines results in folate degradation in the cytosol. Mechanistically, we show that QDPR, an enzyme in tetrahydrobiopterin metabolism, moonlights to repair oxidative damage to tetrahydrofolate (THF). This repair capacity is overwhelmed when cytosolic THF hyperaccumulates in the absence of mitochondrially produced formate, leading to THF degradation. Unexpectedly, we also find that the classic antifolate methotrexate, by inhibiting its well-known target DHFR, causes even more extensive folate degradation in nearly all tested cancer cell lines. These findings shed light on design features of folate metabolism, provide a biochemical basis for clinically observed folate deficiency in QDPR-deficient patients, and reveal a hitherto unknown and unexplored cellular effect of methotrexate.

Published
2018

33. Chromosomal instability drives metastasis through a cytosolic DNA response

Author

Bakhoum, Samuel F, Ngo, Bryan, Laughney, Ashley M, Cavallo, Julie-Ann, Murphy, Charles J, Ly, Peter, Shah, Pragya, Sriram, Roshan K, Watkins, Thomas BK, Taunk, Neil K, Duran, Mercedes, Pauli, Chantal, Shaw, Christine, Chadalavada, Kalyani, Rajasekhar, Vinagolu K, Genovese, Giulio, Venkatesan, Subramanian, Birkbak, Nicolai J, McGranahan, Nicholas, Lundquist, Mark, LaPlant, Quincey, Healey, John H, Elemento, Olivier, Chung, Christine H, Lee, Nancy Y, Imielenski, Marcin, Nanjangud, Gouri, Pe’er, Dana, Cleveland, Don W, Powell, Simon N, Lammerding, Jan, Swanton, Charles, and Cantley, Lewis C

Subjects
Genetics, HIV/AIDS, Aetiology, 2.1 Biological and endogenous factors, Cancer, Animals, Brain Neoplasms, Breast Neoplasms, Carcinoma, Squamous Cell, Cell Line, Chromosomal Instability, Chromosome Segregation, Cytosol, DNA, Neoplasm, Female, Head and Neck Neoplasms, Humans, Inflammation, Membrane Proteins, Mesoderm, Mice, Micronuclei, Chromosome-Defective, NF-kappa B, Neoplasm Metastasis, Nucleotidyltransferases, Xenograft Model Antitumor Assays, General Science & Technology
Abstract

Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs.

Published
2018

34. Post-transcriptional Regulation of De Novo Lipogenesis by mTORC1-S6K1-SRPK2 Signaling

Author

Lee, Gina, Zheng, Yuxiang, Cho, Sungyun, Jang, Cholsoon, England, Christina, Dempsey, Jamie M, Yu, Yonghao, Liu, Xiaolei, He, Long, Cavaliere, Paola M, Chavez, Andre, Zhang, Erik, Isik, Meltem, Couvillon, Anthony, Dephoure, Noah E, Blackwell, T Keith, Yu, Jane J, Rabinowitz, Joshua D, Cantley, Lewis C, and Blenis, John

Subjects
Genetics, Aetiology, 1.1 Normal biological development and functioning, Underpinning research, 2.1 Biological and endogenous factors, Generic health relevance, Animals, Cell Nucleus, Cholesterol, Fatty Acids, Female, Gene Expression Regulation, Heterografts, Humans, Lipogenesis, Mechanistic Target of Rapamycin Complex 1, Mice, Mice, Nude, Neoplasm Transplantation, Protein Serine-Threonine Kinases, RNA Processing, Post-Transcriptional, Ribosomal Protein S6 Kinases, 70-kDa, Signal Transduction, CK1, RNA splicing, RNA stability, S6K1, SR proteins, SRPK2, cancer metabolism, de novo lipid synthesis, mTOR, nonsense-mediated decay, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

mTORC1 is a signal integrator and master regulator of cellular anabolic processes linked to cell growth and survival. Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins. Genome-wide transcriptome analysis reveals that lipid biosynthetic enzymes are among the downstream targets of mTORC1-SRPK2 signaling. Mechanistically, SRPK2 promotes SR protein binding to U1-70K to induce splicing of lipogenic pre-mRNAs. Inhibition of this signaling pathway leads to intron retention of lipogenic genes, which triggers nonsense-mediated mRNA decay. Genetic or pharmacological inhibition of SRPK2 blunts de novo lipid synthesis, thereby suppressing cell growth. These results thus reveal a novel role of mTORC1-SRPK2 signaling in post-transcriptional regulation of lipid metabolism and demonstrate that SRPK2 is a potential therapeutic target for mTORC1-driven metabolic disorders.

Published
2017

35. Cysteine induces mitochondrial reductive stress in glioblastoma through hydrogen peroxide production

Author

Noch, Evan K., primary, Palma, Laura, additional, Yim, Isaiah, additional, Bullen, Nayah, additional, Barnett, Daniel, additional, Walsh, Alexander, additional, Bhinder, Bhavneet, additional, Benedetti, Elisa, additional, Krumsiek, Jan, additional, Gurvitch, Justin, additional, Khwaja, Sumaiyah, additional, Atlas, Daphne, additional, Elemento, Olivier, additional, and Cantley, Lewis C., additional

Published
2024
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36. Pan-cancer proteogenomics characterization of tumor immunity

Author

Petralia, Francesca, primary, Ma, Weiping, additional, Yaron, Tomer M., additional, Caruso, Francesca Pia, additional, Tignor, Nicole, additional, Wang, Joshua M., additional, Charytonowicz, Daniel, additional, Johnson, Jared L., additional, Huntsman, Emily M., additional, Marino, Giacomo B., additional, Calinawan, Anna, additional, Evangelista, John Erol, additional, Selvan, Myvizhi Esai, additional, Chowdhury, Shrabanti, additional, Rykunov, Dmitry, additional, Krek, Azra, additional, Song, Xiaoyu, additional, Turhan, Berk, additional, Christianson, Karen E., additional, Lewis, David A., additional, Deng, Eden Z., additional, Clarke, Daniel J.B., additional, Whiteaker, Jeffrey R., additional, Kennedy, Jacob J., additional, Zhao, Lei, additional, Segura, Rossana Lazcano, additional, Batra, Harsh, additional, Raso, Maria Gabriela, additional, Parra, Edwin Roger, additional, Soundararajan, Rama, additional, Tang, Ximing, additional, Li, Yize, additional, Yi, Xinpei, additional, Satpathy, Shankha, additional, Wang, Ying, additional, Wiznerowicz, Maciej, additional, González-Robles, Tania J., additional, Iavarone, Antonio, additional, Gosline, Sara J.C., additional, Reva, Boris, additional, Robles, Ana I., additional, Nesvizhskii, Alexey I., additional, Mani, D.R., additional, Gillette, Michael A., additional, Klein, Robert J., additional, Cieslik, Marcin, additional, Zhang, Bing, additional, Paulovich, Amanda G., additional, Sebra, Robert, additional, Gümüş, Zeynep H., additional, Hostetter, Galen, additional, Fenyö, David, additional, Omenn, Gilbert S., additional, Cantley, Lewis C., additional, Ma'ayan, Avi, additional, Lazar, Alexander J., additional, Ceccarelli, Michele, additional, Wang, Pei, additional, Abelin, Jennifer, additional, Aguet, François, additional, Akiyama, Yo, additional, An, Eunkyung, additional, Anand, Shankara, additional, Anurag, Meenakshi, additional, Babur, Özgün, additional, Bavarva, Jasmin, additional, Birger, Chet, additional, Birrer, Michael J., additional, Cao, Song, additional, Carr, Steven A., additional, Chan, Daniel W., additional, Chinnaiyan, Arul M., additional, Cho, Hanbyul, additional, Clauser, Karl, additional, Colaprico, Antonio, additional, Zhou, Daniel Cui, additional, da Veiga Leprevost, Felipe, additional, Day, Corbin, additional, Dhanasekaran, Saravana M., additional, Ding, Li, additional, Domagalski, Marcin J., additional, Dou, Yongchao, additional, Druker, Brian J., additional, Edwards, Nathan, additional, Ellis, Matthew J., additional, Foltz, Steven M., additional, Francis, Alicia, additional, Geffen, Yifat, additional, Getz, Gad, additional, Heiman, David I., additional, Hong, Runyu, additional, Hu, Yingwei, additional, Huang, Chen, additional, Jaehnig, Eric J., additional, Jewell, Scott D., additional, Ji, Jiayi, additional, Jiang, Wen, additional, Katsnelson, Lizabeth, additional, Ketchum, Karen A., additional, Kolodziejczak, Iga, additional, Krug, Karsten, additional, Kumar-Sinha, Chandan, additional, Lei, Jonathan T., additional, Liang, Wen-Wei, additional, Liao, Yuxing, additional, Lindgren, Caleb M., additional, Liu, Tao, additional, Liu, Wenke, additional, McDermott, Jason, additional, McKerrow, Wilson, additional, Mesri, Mehdi, additional, Mumphrey, Michael Brodie, additional, Newton, Chelsea J., additional, Oldroyd, Robert, additional, Payne, Samuel H., additional, Pugliese, Pietro, additional, Rodland, Karin D., additional, Rodrigues, Fernanda Martins, additional, Ruggles, Kelly V., additional, Savage, Sara R., additional, Schadt, Eric E., additional, Schnaubelt, Michael, additional, Schraink, Tobias, additional, Schürer, Stephan, additional, Shi, Zhiao, additional, Smith, Richard D., additional, Song, Feng, additional, Song, Yizhe, additional, Stathias, Vasileios, additional, Storrs, Erik P., additional, Tan, Jimin, additional, Terekhanova, Nadezhda V., additional, Thangudu, Ratna R., additional, Thiagarajan, Mathangi, additional, Wang, Liang-Bo, additional, Wen, Bo, additional, Wu, Yige, additional, Wyczalkowski, Matthew A., additional, Yao, Lijun, additional, Li, Qing Kay, additional, Zhang, Hui, additional, Zhang, Qing, additional, Zhang, Xu, additional, and Zhang, Zhen, additional

Published
2024
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37. Dietary fructose improves intestinal cell survival and nutrient absorption

Author

Taylor, Samuel R., Ramsamooj, Shakti, Liang, Roger J., Katti, Alyna, Pozovskiy, Rita, Vasan, Neil, Hwang, Seo-Kyoung, Nahiyaan, Navid, Francoeur, Nancy J., Schatoff, Emma M., Johnson, Jared L., Shah, Manish A., Dannenberg, Andrew J., Sebra, Robert P., Dow, Lukas E., Cantley, Lewis C., Rhee, Kyu Y., and Goncalves, Marcus D.

Published
2021
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40. The PI3K Pathway in Human Disease

Author

Fruman, David A, Chiu, Honyin, Hopkins, Benjamin D, Bagrodia, Shubha, Cantley, Lewis C, and Abraham, Robert T

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Animals, Cell Physiological Phenomena, Humans, Immune System, Neoplasms, Phosphatidylinositol 3-Kinases, Signal Transduction, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Phosphoinositide 3-kinase (PI3K) activity is stimulated by diverse oncogenes and growth factor receptors, and elevated PI3K signaling is considered a hallmark of cancer. Many PI3K pathway-targeted therapies have been tested in oncology trials, resulting in regulatory approval of one isoform-selective inhibitor (idelalisib) for treatment of certain blood cancers and a variety of other agents at different stages of development. In parallel to PI3K research by cancer biologists, investigations in other fields have uncovered exciting and often unpredicted roles for PI3K catalytic and regulatory subunits in normal cell function and in disease. Many of these functions impinge upon oncology by influencing the efficacy and toxicity of PI3K-targeted therapies. Here we provide a perspective on the roles of class I PI3Ks in the regulation of cellular metabolism and in immune system functions, two topics closely intertwined with cancer biology. We also discuss recent progress developing PI3K-targeted therapies for treatment of cancer and other diseases.

Published
2017

41. Fatty acid synthesis is required for breast cancer brain metastasis

Author

Ferraro, Gino B., Ali, Ahmed, Luengo, Alba, Kodack, David P., Deik, Amy, Abbott, Keene L., Bezwada, Divya, Blanc, Landry, Prideaux, Brendan, Jin, Xin, Posada, Jessica M., Chen, Jiang, Chin, Christopher R., Amoozgar, Zohreh, Ferreira, Raphael, Chen, Ivy X., Naxerova, Kamila, Ng, Christopher, Westermark, Anna M., Duquette, Mark, Roberge, Sylvie, Lindeman, Neal I., Lyssiotis, Costas A., Nielsen, Jens, Housman, David E., Duda, Dan G., Brachtel, Elena, Golub, Todd R., Cantley, Lewis C., Asara, John M., Davidson, Shawn M., Fukumura, Dai, Dartois, Véronique A., Clish, Clary B., Jain, Rakesh K., and Vander Heiden, Matthew G.

Published
2021
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42. A FOXO1-dependent transcription network is a targetable vulnerability of mantle cell lymphomas

Author

Jang, Ja-Young, Hwang, Inah, Pan, Heng, Yao, Jun, Alinari, Lapo, Imada, Eddie, Zanettini, Claudio, Kluk, Michael J., Wang, Yizhe, Lee, Yunkyoung, Lin, Hua V., Huang, Xiangao, Liberto, Maurizio Di, Chen, Zhengming, Ballman, Karla V., Cantley, Lewis C., Marchionni, Luigi, Inghirami, Giorgio, Elemento, Olivier, Baiocchi, Robert A., Chen-Kiang, Selina, Belvedere, Sandro, Zheng, Hongwu, and Paik, Jihye

Subjects
Lymphomas -- Genetic aspects -- Development and progression -- Care and treatment, Genetic transcription -- Health aspects, Transcription factors -- Health aspects, Health care industry
Abstract

Targeting lineage-defined transcriptional dependencies has emerged as an effective therapeutic strategy in cancer treatment. Through screening for molecular vulnerabilities of mantle cell lymphoma (MCL), we identified a set of transcription factors (TFs) including FOXO1, EBF1, PAX5, and IRF4 that are essential for MCL propagation. Integrated chromatin immunoprecipitation and sequencing (ChIP-Seq) with transcriptional network reconstruction analysis revealed FOXO1 as a master regulator that acts upstream in the regulatory TF hierarchy. FOXO1 is both necessary and sufficient to drive MCL lineage commitment through supporting the lineage-specific transcription programs. We further show that FOXO1, but not its close paralog FOXO3, can reprogram myeloid leukemia cells and induce B-lineage gene expression. Finally, we demonstrate that cpd10, a small molecule identified from an enriched FOXO1 inhibitor library, induces a robust cytotoxic response in MCL cells in vitro and suppresses MCL progression in vivo. Our findings establish FOXO1 inhibition as a therapeutic strategy targeting lineage-driven transcriptional addiction in MCL., Introduction Mantle cell lymphoma (MCL) is a lethal mature B cell lymphoma manifested by cyclin D1 overexpression due to a t(11;14) (q13;q32) chromosomal translocation and mutations of genes associated with [...]

Published
2022
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43. Identification of SARS-CoV-2 inhibitors using lung and colonic organoids

Author

Han, Yuling, Duan, Xiaohua, Yang, Liuliu, Nilsson-Payant, Benjamin E., Wang, Pengfei, Duan, Fuyu, Tang, Xuming, Yaron, Tomer M., Zhang, Tuo, Uhl, Skyler, Bram, Yaron, Richardson, Chanel, Zhu, Jiajun, Zhao, Zeping, Redmond, David, Houghton, Sean, Nguyen, Duc-Huy T., Xu, Dong, Wang, Xing, Jessurun, Jose, Borczuk, Alain, Huang, Yaoxing, Johnson, Jared L., Liu, Yuru, Xiang, Jenny, Wang, Hui, Cantley, Lewis C., tenOever, Benjamin R., Ho, David D., Pan, Fong Cheng, Evans, Todd, Chen, Huanhuan Joyce, Schwartz, Robert E., and Chen, Shuibing

Published
2021
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44. Targeting the PI5P4K Lipid Kinase Family in Cancer Using Covalent Inhibitors

Author

Sivakumaren, Sindhu Carmen, Shim, Hyeseok, Zhang, Tinghu, Ferguson, Fleur M., Lundquist, Mark R., Browne, Christopher M., Seo, Hyuk-Soo, Paddock, Marcia N., Manz, Theresa D., Jiang, Baishan, Hao, Ming-Feng, Krishnan, Pranav, Wang, Diana G., Yang, T. Jonathan, Kwiatkowski, Nicholas P., Ficarro, Scott B., Cunningham, James M., Marto, Jarrod A., Dhe-Paganon, Sirano, Cantley, Lewis C., and Gray, Nathanael S.

Published
2020
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45. Prioritization schema for immunotherapy clinical trials in glioblastoma

Author

Hodges, Tiffany R, Ferguson, Sherise D, Caruso, Hillary G, Kohanbash, Gary, Zhou, Shouhao, Cloughesy, Timothy F, Berger, Mitchel S, Poste, George H, Khasraw, Mustafa, Ba, Sujuan, Jiang, Tao, Mikkelson, Tom, Yung, WK Alfred, de Groot, John F, Fine, Howard, Cantley, Lewis C, Mellinghoff, Ingo K, Mitchell, Duane A, Okada, Hideho, and Heimberger, Amy B

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Vaccine Related, Immunization, Cancer, Rare Diseases, Brain Cancer, Neurosciences, Brain Disorders, Good Health and Well Being, Clinical trial, glioblastoma, immunotherapy, prioritization, score card, Oncology and carcinogenesis
Abstract

BackgroundEmerging immunotherapeutic strategies for the treatment of glioblastoma (GBM) such as dendritic cell (DC) vaccines, heat shock proteins, peptide vaccines, and adoptive T-cell therapeutics, to name a few, have transitioned from the bench to clinical trials. With upcoming strategies and developing therapeutics, it is challenging to critically evaluate the practical, clinical potential of individual approaches and to advise patients on the most promising clinical trials.MethodsThe authors propose a system to prioritize such therapies in an organized and data-driven fashion. This schema is based on four categories of factors: antigenic target robustness, immune-activation and -effector responses, preclinical vetting, and early evidence of clinical response. Each of these categories is subdivided to focus on the most salient elements for developing a successful immunotherapeutic approach for GBM, and a numerical score is generated.ResultsThe Score Card reveals therapeutics that have the most robust data to support their use, provides a reference prioritization score, and can be applied in a reiterative fashion with emerging data.ConclusionsThe authors hope that this schema will give physicians an evidence-based and rational framework to make the best referral decisions to better guide and serve this patient population.

Published
2016

46. Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton

Author

Hu, Hai, Juvekar, Ashish, Lyssiotis, Costas A, Lien, Evan C, Albeck, John G, Oh, Doogie, Varma, Gopal, Hung, Yin Pun, Ullas, Soumya, Lauring, Josh, Seth, Pankaj, Lundquist, Mark R, Tolan, Dean R, Grant, Aaron K, Needleman, Daniel J, Asara, John M, Cantley, Lewis C, and Wulf, Gerburg M

Subjects
Underpinning research, 1.1 Normal biological development and functioning, Animals, Breast Neoplasms, Cell Line, Tumor, Cytoskeleton, Cytosol, Disease Models, Animal, Epithelial Cells, Fructose-Bisphosphate Aldolase, Glycolysis, Humans, Insulin, Mice, Phosphatidylinositol 3-Kinases, Phosphoinositide-3 Kinase Inhibitors, Signal Transduction, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

The phosphoinositide 3-kinase (PI3K) pathway regulates multiple steps in glucose metabolism and also cytoskeletal functions, such as cell movement and attachment. Here, we show that PI3K directly coordinates glycolysis with cytoskeletal dynamics in an AKT-independent manner. Growth factors or insulin stimulate the PI3K-dependent activation of Rac, leading to disruption of the actin cytoskeleton, release of filamentous actin-bound aldolase A, and an increase in aldolase activity. Consistently, PI3K inhibitors, but not AKT, SGK, or mTOR inhibitors, cause a significant decrease in glycolysis at the step catalyzed by aldolase, while activating PIK3CA mutations have the opposite effect. These results point toward a master regulatory function of PI3K that integrates an epithelial cell's metabolism and its form, shape, and function, coordinating glycolysis with the energy-intensive dynamics of actin remodeling.

Published
2016

47. NAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis

Author

Paul, Swagatika, primary, Sarraf, Shireen A., additional, Nam, Ki Hong, additional, Zavar, Leila, additional, DeFoor, Nicole, additional, Biswas, Sahitya Ranjan, additional, Fritsch, Lauren E., additional, Yaron, Tomer M., additional, Johnson, Jared L., additional, Huntsman, Emily M., additional, Cantley, Lewis C., additional, Ordureau, Alban, additional, and Pickrell, Alicia M., additional

Published
2023
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48. LKB1 suppresses growth and promotes the internalization of EGFR through the PIKFYVE lipid kinase

Author

Ferrarone, John R., primary, Thomas, Jerin, additional, Unni, Arun M., additional, Zheng, Yuxiang, additional, Nagiec, Michal J., additional, Gardner, Eric E., additional, Mashadova, Oksana, additional, Li, Kate, additional, Koundouros, Nikos, additional, Montalbano, Antonino, additional, Mustafa, Meer, additional, Cantley, Lewis C., additional, Blenis, John, additional, Sanjana, Neville E., additional, and Varmus, Harold, additional

Published
2023
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