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1. Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry

Author

Ke, Shizhong, Dang, Fabin, Wang, Lin, Chen, Jia-Yun, Naik, Mandar T., Li, Wenxue, Thavamani, Abhishek, Kim, Nami, Naik, Nandita M., Sui, Huaxiu, Tang, Wei, Qiu, Chenxi, Koikawa, Kazuhiro, Batalini, Felipe, Stern Gatof, Emily, Isaza, Daniela Arango, Patel, Jaymin M., Wang, Xiaodong, Clohessy, John G., Heng, Yujing J., Lahav, Galit, Liu, Yansheng, Gray, Nathanael S., Zhou, Xiao Zhen, Wei, Wenyi, Wulf, Gerburg M., and Lu, Kun Ping

Published
2024
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3. 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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4. Supplementary Table 10 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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5. FIGURE 1 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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6. Supplementary Figure S4 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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7. FIGURE 3 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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8. FIGURE 5 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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9. Supplementary Table 9 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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10. FIGURE 2 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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11. Supplementary Table 7 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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12. Supplementary Table 3 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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13. Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, additional, Alfieri, Roberta, additional, Maymi, Valerie A., additional, Pandell, Nicole, additional, Csizmadia, Eva, additional, Zhang, Junyan, additional, Weetall, Marla, additional, Branstrom, Art, additional, Braccini, Giulia, additional, Cabrera San Millán, Eva, additional, Storti, Barbara, additional, Bizzarri, Ranieri, additional, Kocher, Olivier, additional, Daniela Sanchez Bassères, Daniela S., additional, Welner, Robert S., additional, Magli, Maria Cristina, additional, Merelli, Ivan, additional, Clohessy, John G., additional, Ali, Azhar, additional, Tenen, Daniel G., additional, and Levantini, Elena, additional

Published
2024
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14. Supplementary Table 8 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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15. Supplementary Table 5 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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16. Supplementary Table 2 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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17. Supplementary Table 4 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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18. FIGURE 4 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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19. Data from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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20. Supplementary Table 6 from Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment

Author

Maroni, Giorgia, primary, Krishnan, Indira, primary, Alfieri, Roberta, primary, Maymi, Valerie A., primary, Pandell, Nicole, primary, Csizmadia, Eva, primary, Zhang, Junyan, primary, Weetall, Marla, primary, Branstrom, Art, primary, Braccini, Giulia, primary, Cabrera San Millán, Eva, primary, Storti, Barbara, primary, Bizzarri, Ranieri, primary, Kocher, Olivier, primary, Daniela Sanchez Bassères, Daniela S., primary, Welner, Robert S., primary, Magli, Maria Cristina, primary, Merelli, Ivan, primary, Clohessy, John G., primary, Ali, Azhar, primary, Tenen, Daniel G., primary, and Levantini, Elena, primary

Published
2024
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22. Cholesterol biosynthesis inhibition synergizes with AKT inhibitors in triple-negative breast cancer

Author

Toker, Alex, primary, Hillis, Alissandra L, additional, Martin, Timothy D, additional, Manchester, Haley E, additional, Hogstrom, Jenny M, additional, Zhang, Na, additional, Lecky, Emmalyn, additional, Kozlova, Nina, additional, Persky, Nicole S, additional, Root, David E, additional, Brown, Myles, additional, Cichowski, Karen, additional, Elledge, Stephen J, additional, Muranen, Taru, additional, Fruman, David A, additional, Barry, Simon T, additional, Clohessy, John G, additional, and Madsen, Ralitsa Radostinova, additional

Published
2024
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23. Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma

Author

Tan, Justin L, Fogley, Rachel D, Flynn, Ryan A, Ablain, Julien, Yang, Song, Saint-André, Violaine, Fan, Zi Peng, T., Brian, Laga, Alvaro C, Fujinaga, Koh, Santoriello, Cristina, Greer, Celeste B, Kim, Yoon Jung, Clohessy, John G, Bothmer, Anne, Pandell, Nicole, Avagyan, Serine, Brogie, John E, van Rooijen, Ellen, Hagedorn, Elliott J, Shyh-Chang, Ng, White, Richard M, Price, David H, Pandolfi, Pier Paolo, Peterlin, B Matija, Zhou, Yi, Kim, Tae Hoon, Asara, John M, Chang, Howard Y, Young, Richard A, and Zon, Leonard I

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Immunology, Oncology and Carcinogenesis, Biotechnology, Cancer, Genetics, Aetiology, 2.1 Biological and endogenous factors, Animals, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Melanoma, Melanoma, Experimental, Oncogene Proteins, Positive Transcriptional Elongation Factor B, Pyrimidines, RNA-Binding Proteins, Transcription Factors, Transcription, Genetic, Tumor Suppressor Proteins, Zebrafish, Zebrafish Proteins, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals an important role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma.

Published
2016

24. Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer

Author

Maroni, Giorgia, Bassal, Mahmoud A., Krishnan, Indira, Fhu, Chee Wai, Savova, Virginia, Zilionis, Rapolas, Maymi, Valerie A., Pandell, Nicole, Csizmadia, Eva, Zhang, Junyan, Storti, Barbara, Castaño, Julio, Panella, Riccardo, Li, Jia, Gustafson, Corinne E., Fox, Sam, Levy, Rachel D., Meyerovitz, Claire V., Tramontozzi, Peter J., Vermilya, Kimberly, De Rienzo, Assunta, Crucitta, Stefania, Bassères, Daniela S., Weetall, Marla, Branstrom, Art, Giorgetti, Alessandra, Ciampi, Raffaele, Del Re, Marzia, Danesi, Romano, Bizzarri, Ranieri, Yang, Henry, Kocher, Olivier, Klein, Allon M., Welner, Robert S., Bueno, Raphael, Magli, Maria Cristina, Clohessy, John G., Ali, Azhar, Tenen, Daniel G., and Levantini, Elena

Published
2021
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26. Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry.

Author

Ke, Shizhong, Dang, Fabin, Wang, Lin, Chen, Jia-Yun, Naik, Mandar T., Li, Wenxue, Thavamani, Abhishek, Kim, Nami, Naik, Nandita M., Sui, Huaxiu, Tang, Wei, Qiu, Chenxi, Koikawa, Kazuhiro, Batalini, Felipe, Stern Gatof, Emily, Isaza, Daniela Arango, Patel, Jaymin M., Wang, Xiaodong, Clohessy, John G., and Heng, Yujing J.

Abstract

Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/CCDH1) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/CCDH1 activity to treat cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)-catalyzed phosphorylation-dependent cis-trans prolyl isomerization drives tumor malignancy. However, the mechanisms controlling its protein turnover remain elusive. Through proteomic screens and structural characterizations, we identify a reciprocal antagonism of PIN1-APC/CCDH1 mediated by domain-oriented phosphorylation-dependent dual interactions as a fundamental mechanism governing mitotic protein stability and cell-cycle entry. Remarkably, combined PIN1 and cyclin-dependent protein kinases (CDKs) inhibition creates a positive feedback loop of PIN1 inhibition and APC/CCDH1 activation to irreversibly degrade PIN1 and other crucial mitotic proteins, which force permanent cell-cycle exit and trigger anti-tumor immunity, translating into synergistic efficacy against triple-negative breast cancer. Unveiling the regulation of mitotic protein degradation is crucial for cancer therapy. Here, the authors reveal that a reciprocal inhibition of PIN1-APC/CCDH1 controls the cell cycle and mitotic protein degradation, offering a synergistic anti-tumor strategy. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Germline NPM1 mutations lead to altered rRNA 2′-O-methylation and cause dyskeratosis congenita

Author

Nachmani, Daphna, Bothmer, Anne H., Grisendi, Silvia, Mele, Aldo, Bothmer, Dietmar, Lee, Jonathan D., Monteleone, Emanuele, Cheng, Ke, Zhang, Yang, Bester, Assaf C., Guzzetti, Alison, Mitchell, Caitlin A., Mendez, Lourdes M., Pozdnyakova, Olga, Sportoletti, Paolo, Martelli, Maria-Paola, Vulliamy, Tom J., Safra, Modi, Schwartz, Schraga, Luzzatto, Lucio, Bluteau, Olivier, Soulier, Jean, Darnell, Robert B., Falini, Brunangelo, Dokal, Inderjeet, Ito, Keisuke, Clohessy, John G., and Pandolfi, Pier Paolo

Published
2019
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28. Intragenic antagonistic roles of protein and circRNA in tumorigenesis

Author

Guarnerio, Jlenia, Zhang, Yang, Cheloni, Giulia, Panella, Riccardo, Mae Katon, Jesse, Simpson, Mark, Matsumoto, Akinobu, Papa, Antonella, Loretelli, Cristian, Petri, Andreas, Kauppinen, Sakari, Garbutt, Cassandra, Nielsen, Gunnlaugur Petur, Deshpande, Vikram, Castillo-Martin, Mireia, Cordon-Cardo, Carlos, Dimitrios, Spentzos, Clohessy, John G., Batish, Mona, and Pandolfi, Pier Paolo

Published
2019
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29. WWP1 inactivation enhances efficacy of PI3K inhibitors while suppressing their toxicities in breast cancer models

Author

Kishikawa, Takahiro, Higuchi, Hiroshi, Wang, Limei, Panch, Nivedita, Maymi, Valerie, Best, Sachem, Lee, Samuel, Notoya, Genso, Toker, Alex, Matesic, Lydia E., Wulf, Gerburg M., Wei, Wenyi, Otsuka, Motoyuki, Koike, Kazuhiko, Clohessy, John G., Lee, Yu-Ru, and Pandolfi, Pier Paolo

Subjects
Gene mutations -- Health aspects, Phosphotransferases -- Health aspects, Breast cancer -- Genetic aspects -- Development and progression -- Care and treatment, Health care industry
Abstract

Activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is a pervasive event in tumorigenesis due to PI3K mutation and dysfunction of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Pharmacological inhibition of PI3K has resulted in variable clinical outcomes, however, raising questions regarding the possible mechanisms of unresponsiveness and resistance to treatment. WWP1 is an oncogenic HECT-type ubiquitin E3 ligase frequently amplified and mutated in multiple cancers, as well as in the germ lines of patients predisposed to cancer, and was recently found to activate PI3K signaling through PTEN inactivation. Here, we demonstrate that PTEN dissociated from the plasma membrane upon treatment with PI3K inhibitors through WWP1 activation, whereas WWP1 genetic or pharmacological inhibition restored PTEN membrane localization, synergizing with PI3K inhibitors to suppress tumor growth both in vitro and in vivo. Furthermore, we demonstrate that WWP1 inhibition attenuated hyperglycemia and the consequent insulin feedback, which is a major tumor-promoting side effect of PI3K inhibitors. Mechanistically, we found that AMPKa2 was ubiquitinated and, in turn, inhibited in its activatory phosphorylation by WWP1, whereas WWP1 inhibition facilitated AMPK[alpha]2 activity in the muscle to compensate for the reduction in glucose uptake observed upon PI3K inhibition. Thus, our identification of the cell-autonomous and systemic roles of WWP1 inhibition expands the therapeutic potential of PI3K inhibitors and reveals new avenues of combination cancer therapy., Introduction Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in regulating various biological functions, including cell growth, survival, differentiation, metabolism, and motility. Dysregulation of the PI3K signaling pathway is one of [...]

Published
2021
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31. The Tug1 lncRNA locus is essential for male fertility

Author

Lewandowski, Jordan P., Dumbović, Gabrijela, Watson, Audrey R., Hwang, Taeyoung, Jacobs-Palmer, Emily, Chang, Nydia, Much, Christian, Turner, Kyle M., Kirby, Christopher, Rubinstein, Nimrod D., Groff, Abigail F., Liapis, Steve C., Gerhardinger, Chiara, Bester, Assaf, Pandolfi, Pier Paolo, Clohessy, John G., Hoekstra, Hopi E., Sauvageau, Martin, and Rinn, John L.

Published
2020
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32. Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms

Author

Bezzi, Marco, Seitzer, Nina, Ishikawa, Tomoki, Reschke, Markus, Chen, Ming, Wang, Guocan, Mitchell, Caitlin, Ng, Christopher, Katon, Jesse, Lunardi, Andrea, Signoretti, Sabina, Clohessy, John G, Zhang, Jiangwen, and Pandolfi, Pier Paolo

Subjects
Tumors -- Development and progression -- Genetic aspects -- Research, Immune response -- Physiological aspects -- Genetic aspects -- Research, Cancer metastasis -- Development and progression -- Genetic aspects -- Research, Biological sciences, Health
Abstract

Multiple immune-cell types can infiltrate tumors and promote progression and metastasis through different mechanisms, including immunosuppression. How distinct genetic alterations in tumors affect the composition of the immune landscape is currently unclear. Here, we characterized the immune-cell composition of prostate cancers driven by the loss of the critical tumor suppressor gene Pten, either alone or in combination with the loss of Trp53, Zbtb7a or Pml. We observed a striking quantitative and qualitative heterogeneity that was directly dependent on the specific genetic events in the tumor and ranged from 'cold', noninflamed tumors to massively infiltrated landscapes--results with important therapeutic implications. Further, we showed these qualitative differences in transcriptomic analysis of human prostate cancer samples. These data suggest that patient stratification on the basis of integrated genotypic-immunophenotypic analyses may be necessary for successful clinical trials and tailored precision immunological therapies., Author(s): Marco Bezzi [1]; Nina Seitzer [1]; Tomoki Ishikawa [1]; Markus Reschke [1]; Ming Chen [1]; Guocan Wang [1]; Caitlin Mitchell [1]; Christopher Ng [1]; Jesse Katon [1]; Andrea Lunardi [...]

Published
2018
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33. An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer

Author

Chen, Ming, Zhang, Jiangwen, Sampieri, Katia, Clohessy, John G., Mendez, Lourdes, Gonzalez-Billalabeitia, Enrique, Liu, Xue-Song, Lee, Yu-Ru, Fung, Jacqueline, Katon, Jesse M., Menon, Archita Venugopal, Webster, Kaitlyn A., Ng, Christopher, Palumbieri, Maria Dilia, Diolombi, Moussa S., Breitkopf, Susanne B., Teruya-Feldstein, Julie, Signoretti, Sabina, Bronson, Roderick T., Asara, John M., Castillo-Martin, Mireia, Cordon-Cardo, Carlos, and Pandolfi, Pier Paolo

Published
2018
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34. Data from Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity

Author

Patnaik, Akash, primary, Swanson, Kenneth D., primary, Csizmadia, Eva, primary, Solanki, Aniruddh, primary, Landon-Brace, Natalie, primary, Gehring, Marina P., primary, Helenius, Katja, primary, Olson, Brian M., primary, Pyzer, Athalia R., primary, Wang, Lily C., primary, Elemento, Olivier, primary, Novak, Jesse, primary, Thornley, Thomas B., primary, Asara, John M., primary, Montaser, Laleh, primary, Timmons, Joshua J., primary, Morgan, Todd M., primary, Wang, Yugang, primary, Levantini, Elena, primary, Clohessy, John G., primary, Kelly, Kathleen, primary, Pandolfi, Pier Paolo, primary, Rosenblatt, Jacalyn M., primary, Avigan, David E., primary, Ye, Huihui, primary, Karp, Jeffrey M., primary, Signoretti, Sabina, primary, Balk, Steven P., primary, and Cantley, Lewis C., primary

Published
2023
Full Text
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35. Supplementary Figure 1 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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36. Supplementary Figure 5 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
Full Text
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37. Data from In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K–AKT Signaling at Endosomes

Author

Li Chew, Chen, primary, Lunardi, Andrea, primary, Gulluni, Federico, primary, Ruan, Daniel T., primary, Chen, Ming, primary, Salmena, Leonardo, primary, Nishino, Michiya, primary, Papa, Antonella, primary, Ng, Christopher, primary, Fung, Jacqueline, primary, Clohessy, John G., primary, Sasaki, Junko, primary, Sasaki, Takehiko, primary, Bronson, Roderick T., primary, Hirsch, Emilio, primary, and Pandolfi, Pier Paolo, primary

Published
2023
Full Text
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38. Supplementary Figure Legends from Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity

Author

Patnaik, Akash, primary, Swanson, Kenneth D., primary, Csizmadia, Eva, primary, Solanki, Aniruddh, primary, Landon-Brace, Natalie, primary, Gehring, Marina P., primary, Helenius, Katja, primary, Olson, Brian M., primary, Pyzer, Athalia R., primary, Wang, Lily C., primary, Elemento, Olivier, primary, Novak, Jesse, primary, Thornley, Thomas B., primary, Asara, John M., primary, Montaser, Laleh, primary, Timmons, Joshua J., primary, Morgan, Todd M., primary, Wang, Yugang, primary, Levantini, Elena, primary, Clohessy, John G., primary, Kelly, Kathleen, primary, Pandolfi, Pier Paolo, primary, Rosenblatt, Jacalyn M., primary, Avigan, David E., primary, Ye, Huihui, primary, Karp, Jeffrey M., primary, Signoretti, Sabina, primary, Balk, Steven P., primary, and Cantley, Lewis C., primary

Published
2023
Full Text
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39. Supplementary Figure 1 from Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity

Author

Patnaik, Akash, primary, Swanson, Kenneth D., primary, Csizmadia, Eva, primary, Solanki, Aniruddh, primary, Landon-Brace, Natalie, primary, Gehring, Marina P., primary, Helenius, Katja, primary, Olson, Brian M., primary, Pyzer, Athalia R., primary, Wang, Lily C., primary, Elemento, Olivier, primary, Novak, Jesse, primary, Thornley, Thomas B., primary, Asara, John M., primary, Montaser, Laleh, primary, Timmons, Joshua J., primary, Morgan, Todd M., primary, Wang, Yugang, primary, Levantini, Elena, primary, Clohessy, John G., primary, Kelly, Kathleen, primary, Pandolfi, Pier Paolo, primary, Rosenblatt, Jacalyn M., primary, Avigan, David E., primary, Ye, Huihui, primary, Karp, Jeffrey M., primary, Signoretti, Sabina, primary, Balk, Steven P., primary, and Cantley, Lewis C., primary

Published
2023
Full Text
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40. Supplementary Figure 5 from Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity

Author

Patnaik, Akash, primary, Swanson, Kenneth D., primary, Csizmadia, Eva, primary, Solanki, Aniruddh, primary, Landon-Brace, Natalie, primary, Gehring, Marina P., primary, Helenius, Katja, primary, Olson, Brian M., primary, Pyzer, Athalia R., primary, Wang, Lily C., primary, Elemento, Olivier, primary, Novak, Jesse, primary, Thornley, Thomas B., primary, Asara, John M., primary, Montaser, Laleh, primary, Timmons, Joshua J., primary, Morgan, Todd M., primary, Wang, Yugang, primary, Levantini, Elena, primary, Clohessy, John G., primary, Kelly, Kathleen, primary, Pandolfi, Pier Paolo, primary, Rosenblatt, Jacalyn M., primary, Avigan, David E., primary, Ye, Huihui, primary, Karp, Jeffrey M., primary, Signoretti, Sabina, primary, Balk, Steven P., primary, and Cantley, Lewis C., primary

Published
2023
Full Text
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41. Supplementary Figure 3 from In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K–AKT Signaling at Endosomes

Author

Li Chew, Chen, primary, Lunardi, Andrea, primary, Gulluni, Federico, primary, Ruan, Daniel T., primary, Chen, Ming, primary, Salmena, Leonardo, primary, Nishino, Michiya, primary, Papa, Antonella, primary, Ng, Christopher, primary, Fung, Jacqueline, primary, Clohessy, John G., primary, Sasaki, Junko, primary, Sasaki, Takehiko, primary, Bronson, Roderick T., primary, Hirsch, Emilio, primary, and Pandolfi, Pier Paolo, primary

Published
2023
Full Text
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42. Supplementary Figure 2 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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43. Supplementary Materials and Methods, Figure Legends from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
Full Text
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44. Supplementary Figure 3 from Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity

Author

Patnaik, Akash, primary, Swanson, Kenneth D., primary, Csizmadia, Eva, primary, Solanki, Aniruddh, primary, Landon-Brace, Natalie, primary, Gehring, Marina P., primary, Helenius, Katja, primary, Olson, Brian M., primary, Pyzer, Athalia R., primary, Wang, Lily C., primary, Elemento, Olivier, primary, Novak, Jesse, primary, Thornley, Thomas B., primary, Asara, John M., primary, Montaser, Laleh, primary, Timmons, Joshua J., primary, Morgan, Todd M., primary, Wang, Yugang, primary, Levantini, Elena, primary, Clohessy, John G., primary, Kelly, Kathleen, primary, Pandolfi, Pier Paolo, primary, Rosenblatt, Jacalyn M., primary, Avigan, David E., primary, Ye, Huihui, primary, Karp, Jeffrey M., primary, Signoretti, Sabina, primary, Balk, Steven P., primary, and Cantley, Lewis C., primary

Published
2023
Full Text
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45. Supplementary Figure Legends from In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K–AKT Signaling at Endosomes

Author

Li Chew, Chen, primary, Lunardi, Andrea, primary, Gulluni, Federico, primary, Ruan, Daniel T., primary, Chen, Ming, primary, Salmena, Leonardo, primary, Nishino, Michiya, primary, Papa, Antonella, primary, Ng, Christopher, primary, Fung, Jacqueline, primary, Clohessy, John G., primary, Sasaki, Junko, primary, Sasaki, Takehiko, primary, Bronson, Roderick T., primary, Hirsch, Emilio, primary, and Pandolfi, Pier Paolo, primary

Published
2023
Full Text
View/download PDF

46. Supplementary Figure 5 from In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K–AKT Signaling at Endosomes

Author

Li Chew, Chen, primary, Lunardi, Andrea, primary, Gulluni, Federico, primary, Ruan, Daniel T., primary, Chen, Ming, primary, Salmena, Leonardo, primary, Nishino, Michiya, primary, Papa, Antonella, primary, Ng, Christopher, primary, Fung, Jacqueline, primary, Clohessy, John G., primary, Sasaki, Junko, primary, Sasaki, Takehiko, primary, Bronson, Roderick T., primary, Hirsch, Emilio, primary, and Pandolfi, Pier Paolo, primary

Published
2023
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47. Supplementary Data from Cabozantinib Unlocks Efficient In Vivo Targeted Delivery of Neutrophil-Loaded Nanoparticles into Murine Prostate Tumors

Author

Chaudagar, Kiranj Kishor, primary, Landon-Brace, Natalie, primary, Solanki, Aniruddh, primary, Hieromnimon, Hanna M., primary, Hegermiller, Emma, primary, Li, Wen, primary, Shao, Yue, primary, Joseph, John, primary, Wilkins, Devan J., primary, Bynoe, Kaela M., primary, Li, Xiang-Ling, primary, Clohessy, John G., primary, Ullas, Soumya, primary, Karp, Jeffrey M., primary, and Patnaik, Akash, primary

Published
2023
Full Text
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48. Supplementary Figure 2 from In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K–AKT Signaling at Endosomes

Author

Li Chew, Chen, primary, Lunardi, Andrea, primary, Gulluni, Federico, primary, Ruan, Daniel T., primary, Chen, Ming, primary, Salmena, Leonardo, primary, Nishino, Michiya, primary, Papa, Antonella, primary, Ng, Christopher, primary, Fung, Jacqueline, primary, Clohessy, John G., primary, Sasaki, Junko, primary, Sasaki, Takehiko, primary, Bronson, Roderick T., primary, Hirsch, Emilio, primary, and Pandolfi, Pier Paolo, primary

Published
2023
Full Text
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49. Data from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
Full Text
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50. Supplementary Figure 6 from Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity

Author

Patnaik, Akash, primary, Swanson, Kenneth D., primary, Csizmadia, Eva, primary, Solanki, Aniruddh, primary, Landon-Brace, Natalie, primary, Gehring, Marina P., primary, Helenius, Katja, primary, Olson, Brian M., primary, Pyzer, Athalia R., primary, Wang, Lily C., primary, Elemento, Olivier, primary, Novak, Jesse, primary, Thornley, Thomas B., primary, Asara, John M., primary, Montaser, Laleh, primary, Timmons, Joshua J., primary, Morgan, Todd M., primary, Wang, Yugang, primary, Levantini, Elena, primary, Clohessy, John G., primary, Kelly, Kathleen, primary, Pandolfi, Pier Paolo, primary, Rosenblatt, Jacalyn M., primary, Avigan, David E., primary, Ye, Huihui, primary, Karp, Jeffrey M., primary, Signoretti, Sabina, primary, Balk, Steven P., primary, and Cantley, Lewis C., primary

Published
2023
Full Text
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