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32 results on '"Kim, Carla"'

1. CUT&RUN Supplementary Data from Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung

Author

Concepcion, Carla P., primary, Ma, Sai, primary, LaFave, Lindsay M., primary, Bhutkar, Arjun, primary, Liu, Manyuan, primary, DeAngelo, Lydia P., primary, Kim, Jonathan Y., primary, Del Priore, Isabella, primary, Schoenfeld, Adam J., primary, Miller, Manon, primary, Kartha, Vinay K., primary, Westcott, Peter M.K., primary, Sánchez-Rivera, Francisco J., primary, Meli, Kevin, primary, Gupta, Manav, primary, Bronson, Roderick T., primary, Riely, Gregory J., primary, Rekhtman, Natasha, primary, Rudin, Charles M., primary, Kim, Carla F., primary, Regev, Aviv, primary, Buenrostro, Jason D., primary, and Jacks, Tyler, primary

Published
2023
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2. Supplementary Table S1 from Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung

Author

Concepcion, Carla P., primary, Ma, Sai, primary, LaFave, Lindsay M., primary, Bhutkar, Arjun, primary, Liu, Manyuan, primary, DeAngelo, Lydia P., primary, Kim, Jonathan Y., primary, Del Priore, Isabella, primary, Schoenfeld, Adam J., primary, Miller, Manon, primary, Kartha, Vinay K., primary, Westcott, Peter M.K., primary, Sánchez-Rivera, Francisco J., primary, Meli, Kevin, primary, Gupta, Manav, primary, Bronson, Roderick T., primary, Riely, Gregory J., primary, Rekhtman, Natasha, primary, Rudin, Charles M., primary, Kim, Carla F., primary, Regev, Aviv, primary, Buenrostro, Jason D., primary, and Jacks, Tyler, primary

Published
2023
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3. Supplementary Figures S1-S7 from Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung

Author

Concepcion, Carla P., primary, Ma, Sai, primary, LaFave, Lindsay M., primary, Bhutkar, Arjun, primary, Liu, Manyuan, primary, DeAngelo, Lydia P., primary, Kim, Jonathan Y., primary, Del Priore, Isabella, primary, Schoenfeld, Adam J., primary, Miller, Manon, primary, Kartha, Vinay K., primary, Westcott, Peter M.K., primary, Sánchez-Rivera, Francisco J., primary, Meli, Kevin, primary, Gupta, Manav, primary, Bronson, Roderick T., primary, Riely, Gregory J., primary, Rekhtman, Natasha, primary, Rudin, Charles M., primary, Kim, Carla F., primary, Regev, Aviv, primary, Buenrostro, Jason D., primary, and Jacks, Tyler, primary

Published
2023
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4. RNA-seq (cell line) Supplementary Data from Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung

Author

Concepcion, Carla P., primary, Ma, Sai, primary, LaFave, Lindsay M., primary, Bhutkar, Arjun, primary, Liu, Manyuan, primary, DeAngelo, Lydia P., primary, Kim, Jonathan Y., primary, Del Priore, Isabella, primary, Schoenfeld, Adam J., primary, Miller, Manon, primary, Kartha, Vinay K., primary, Westcott, Peter M.K., primary, Sánchez-Rivera, Francisco J., primary, Meli, Kevin, primary, Gupta, Manav, primary, Bronson, Roderick T., primary, Riely, Gregory J., primary, Rekhtman, Natasha, primary, Rudin, Charles M., primary, Kim, Carla F., primary, Regev, Aviv, primary, Buenrostro, Jason D., primary, and Jacks, Tyler, primary

Published
2023
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5. RNA-seq (primary tumors) Supplementary Data from Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung

Author

Concepcion, Carla P., primary, Ma, Sai, primary, LaFave, Lindsay M., primary, Bhutkar, Arjun, primary, Liu, Manyuan, primary, DeAngelo, Lydia P., primary, Kim, Jonathan Y., primary, Del Priore, Isabella, primary, Schoenfeld, Adam J., primary, Miller, Manon, primary, Kartha, Vinay K., primary, Westcott, Peter M.K., primary, Sánchez-Rivera, Francisco J., primary, Meli, Kevin, primary, Gupta, Manav, primary, Bronson, Roderick T., primary, Riely, Gregory J., primary, Rekhtman, Natasha, primary, Rudin, Charles M., primary, Kim, Carla F., primary, Regev, Aviv, primary, Buenrostro, Jason D., primary, and Jacks, Tyler, primary

Published
2023
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6. Bulk ATAC-seq Supplementary Data from Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung

Author

Concepcion, Carla P., primary, Ma, Sai, primary, LaFave, Lindsay M., primary, Bhutkar, Arjun, primary, Liu, Manyuan, primary, DeAngelo, Lydia P., primary, Kim, Jonathan Y., primary, Del Priore, Isabella, primary, Schoenfeld, Adam J., primary, Miller, Manon, primary, Kartha, Vinay K., primary, Westcott, Peter M.K., primary, Sánchez-Rivera, Francisco J., primary, Meli, Kevin, primary, Gupta, Manav, primary, Bronson, Roderick T., primary, Riely, Gregory J., primary, Rekhtman, Natasha, primary, Rudin, Charles M., primary, Kim, Carla F., primary, Regev, Aviv, primary, Buenrostro, Jason D., primary, and Jacks, Tyler, primary

Published
2023
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7. Data from Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung

Author

Concepcion, Carla P., primary, Ma, Sai, primary, LaFave, Lindsay M., primary, Bhutkar, Arjun, primary, Liu, Manyuan, primary, DeAngelo, Lydia P., primary, Kim, Jonathan Y., primary, Del Priore, Isabella, primary, Schoenfeld, Adam J., primary, Miller, Manon, primary, Kartha, Vinay K., primary, Westcott, Peter M.K., primary, Sánchez-Rivera, Francisco J., primary, Meli, Kevin, primary, Gupta, Manav, primary, Bronson, Roderick T., primary, Riely, Gregory J., primary, Rekhtman, Natasha, primary, Rudin, Charles M., primary, Kim, Carla F., primary, Regev, Aviv, primary, Buenrostro, Jason D., primary, and Jacks, Tyler, primary

Published
2023
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8. Data from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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9. Supplementary Figures S1 - S5, Tables S1 - S2 from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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10. Supplementary Table 3 from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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11. Supplementary Methods from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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12. Supplementary Table 5 from BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., primary, Fahey, Caroline G., primary, Keshishian, Hasmik, primary, Bhutkar, Arjun, primary, Brainson, Christine F., primary, Sanchez-Rivera, Francisco J., primary, Pessina, Patrizia, primary, Kim, Jonathan Y., primary, Simoneau, Antoine, primary, Paschini, Margherita, primary, Beytagh, Mary C., primary, Stanclift, Caroline R., primary, Schenone, Monica, primary, Mani, D.R., primary, Li, Chendi, primary, Oh, Audris, primary, Li, Fei, primary, Hu, Hai, primary, Karatza, Angeliki, primary, Bronson, Roderick T., primary, Shaw, Alice T., primary, Hata, Aaron N., primary, Wong, Kwok-Kin, primary, Zou, Lee, primary, Carr, Steven A., primary, Jacks, Tyler, primary, and Kim, Carla F., primary

Published
2023
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13. Figure S4 from BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., primary, Fahey, Caroline G., primary, Keshishian, Hasmik, primary, Bhutkar, Arjun, primary, Brainson, Christine F., primary, Sanchez-Rivera, Francisco J., primary, Pessina, Patrizia, primary, Kim, Jonathan Y., primary, Simoneau, Antoine, primary, Paschini, Margherita, primary, Beytagh, Mary C., primary, Stanclift, Caroline R., primary, Schenone, Monica, primary, Mani, D.R., primary, Li, Chendi, primary, Oh, Audris, primary, Li, Fei, primary, Hu, Hai, primary, Karatza, Angeliki, primary, Bronson, Roderick T., primary, Shaw, Alice T., primary, Hata, Aaron N., primary, Wong, Kwok-Kin, primary, Zou, Lee, primary, Carr, Steven A., primary, Jacks, Tyler, primary, and Kim, Carla F., primary

Published
2023
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14. Supplementary Table 3 from BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., primary, Fahey, Caroline G., primary, Keshishian, Hasmik, primary, Bhutkar, Arjun, primary, Brainson, Christine F., primary, Sanchez-Rivera, Francisco J., primary, Pessina, Patrizia, primary, Kim, Jonathan Y., primary, Simoneau, Antoine, primary, Paschini, Margherita, primary, Beytagh, Mary C., primary, Stanclift, Caroline R., primary, Schenone, Monica, primary, Mani, D.R., primary, Li, Chendi, primary, Oh, Audris, primary, Li, Fei, primary, Hu, Hai, primary, Karatza, Angeliki, primary, Bronson, Roderick T., primary, Shaw, Alice T., primary, Hata, Aaron N., primary, Wong, Kwok-Kin, primary, Zou, Lee, primary, Carr, Steven A., primary, Jacks, Tyler, primary, and Kim, Carla F., primary

Published
2023
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15. Supplementary Table 2 from BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., primary, Fahey, Caroline G., primary, Keshishian, Hasmik, primary, Bhutkar, Arjun, primary, Brainson, Christine F., primary, Sanchez-Rivera, Francisco J., primary, Pessina, Patrizia, primary, Kim, Jonathan Y., primary, Simoneau, Antoine, primary, Paschini, Margherita, primary, Beytagh, Mary C., primary, Stanclift, Caroline R., primary, Schenone, Monica, primary, Mani, D.R., primary, Li, Chendi, primary, Oh, Audris, primary, Li, Fei, primary, Hu, Hai, primary, Karatza, Angeliki, primary, Bronson, Roderick T., primary, Shaw, Alice T., primary, Hata, Aaron N., primary, Wong, Kwok-Kin, primary, Zou, Lee, primary, Carr, Steven A., primary, Jacks, Tyler, primary, and Kim, Carla F., primary

Published
2023
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16. Supplementary Table 4 from BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., primary, Fahey, Caroline G., primary, Keshishian, Hasmik, primary, Bhutkar, Arjun, primary, Brainson, Christine F., primary, Sanchez-Rivera, Francisco J., primary, Pessina, Patrizia, primary, Kim, Jonathan Y., primary, Simoneau, Antoine, primary, Paschini, Margherita, primary, Beytagh, Mary C., primary, Stanclift, Caroline R., primary, Schenone, Monica, primary, Mani, D.R., primary, Li, Chendi, primary, Oh, Audris, primary, Li, Fei, primary, Hu, Hai, primary, Karatza, Angeliki, primary, Bronson, Roderick T., primary, Shaw, Alice T., primary, Hata, Aaron N., primary, Wong, Kwok-Kin, primary, Zou, Lee, primary, Carr, Steven A., primary, Jacks, Tyler, primary, and Kim, Carla F., primary

Published
2023
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17. Data from BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., primary, Fahey, Caroline G., primary, Keshishian, Hasmik, primary, Bhutkar, Arjun, primary, Brainson, Christine F., primary, Sanchez-Rivera, Francisco J., primary, Pessina, Patrizia, primary, Kim, Jonathan Y., primary, Simoneau, Antoine, primary, Paschini, Margherita, primary, Beytagh, Mary C., primary, Stanclift, Caroline R., primary, Schenone, Monica, primary, Mani, D.R., primary, Li, Chendi, primary, Oh, Audris, primary, Li, Fei, primary, Hu, Hai, primary, Karatza, Angeliki, primary, Bronson, Roderick T., primary, Shaw, Alice T., primary, Hata, Aaron N., primary, Wong, Kwok-Kin, primary, Zou, Lee, primary, Carr, Steven A., primary, Jacks, Tyler, primary, and Kim, Carla F., primary

Published
2023
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18. Supplementary Table 1 from BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., primary, Fahey, Caroline G., primary, Keshishian, Hasmik, primary, Bhutkar, Arjun, primary, Brainson, Christine F., primary, Sanchez-Rivera, Francisco J., primary, Pessina, Patrizia, primary, Kim, Jonathan Y., primary, Simoneau, Antoine, primary, Paschini, Margherita, primary, Beytagh, Mary C., primary, Stanclift, Caroline R., primary, Schenone, Monica, primary, Mani, D.R., primary, Li, Chendi, primary, Oh, Audris, primary, Li, Fei, primary, Hu, Hai, primary, Karatza, Angeliki, primary, Bronson, Roderick T., primary, Shaw, Alice T., primary, Hata, Aaron N., primary, Wong, Kwok-Kin, primary, Zou, Lee, primary, Carr, Steven A., primary, Jacks, Tyler, primary, and Kim, Carla F., primary

Published
2023
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19. Titles for supplementary tables from BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., primary, Fahey, Caroline G., primary, Keshishian, Hasmik, primary, Bhutkar, Arjun, primary, Brainson, Christine F., primary, Sanchez-Rivera, Francisco J., primary, Pessina, Patrizia, primary, Kim, Jonathan Y., primary, Simoneau, Antoine, primary, Paschini, Margherita, primary, Beytagh, Mary C., primary, Stanclift, Caroline R., primary, Schenone, Monica, primary, Mani, D.R., primary, Li, Chendi, primary, Oh, Audris, primary, Li, Fei, primary, Hu, Hai, primary, Karatza, Angeliki, primary, Bronson, Roderick T., primary, Shaw, Alice T., primary, Hata, Aaron N., primary, Wong, Kwok-Kin, primary, Zou, Lee, primary, Carr, Steven A., primary, Jacks, Tyler, primary, and Kim, Carla F., primary

Published
2023
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20. Figure legends for supplementary figures from BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., primary, Fahey, Caroline G., primary, Keshishian, Hasmik, primary, Bhutkar, Arjun, primary, Brainson, Christine F., primary, Sanchez-Rivera, Francisco J., primary, Pessina, Patrizia, primary, Kim, Jonathan Y., primary, Simoneau, Antoine, primary, Paschini, Margherita, primary, Beytagh, Mary C., primary, Stanclift, Caroline R., primary, Schenone, Monica, primary, Mani, D.R., primary, Li, Chendi, primary, Oh, Audris, primary, Li, Fei, primary, Hu, Hai, primary, Karatza, Angeliki, primary, Bronson, Roderick T., primary, Shaw, Alice T., primary, Hata, Aaron N., primary, Wong, Kwok-Kin, primary, Zou, Lee, primary, Carr, Steven A., primary, Jacks, Tyler, primary, and Kim, Carla F., primary

Published
2023
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22. SMARCA4 inactivation promotes lineage-specific transformation and early metastatic features in the lung

Author

Massachusetts Institute of Technology. Department of Biology, Concepcion, Carla P, Ma, Sai, LaFave, Lindsay M, Bhutkar, Arjun, Liu, Manyuan, DeAngelo, Lydia P, Kim, Jonathan Y, Del Priore, Isabella, Schoenfeld, Adam J, Miller, Manon, Kartha, Vinay K, Westcott, Peter MK, Sánchez-Rivera, Francisco J, Meli, Kevin, Gupta, Manav, Bronson, Roderick T, Riely, Gregory J, Rekhtman, Natasha, Rudin, Charles M, Kim, Carla F, Regev, Aviv, Buenrostro, Jason D, Jacks, Tyler, Massachusetts Institute of Technology. Department of Biology, Concepcion, Carla P, Ma, Sai, LaFave, Lindsay M, Bhutkar, Arjun, Liu, Manyuan, DeAngelo, Lydia P, Kim, Jonathan Y, Del Priore, Isabella, Schoenfeld, Adam J, Miller, Manon, Kartha, Vinay K, Westcott, Peter MK, Sánchez-Rivera, Francisco J, Meli, Kevin, Gupta, Manav, Bronson, Roderick T, Riely, Gregory J, Rekhtman, Natasha, Rudin, Charles M, Kim, Carla F, Regev, Aviv, Buenrostro, Jason D, and Jacks, Tyler

Abstract

Abstract SMARCA4/BRG1 encodes for one of two mutually exclusive ATPases present in mammalian SWI/SNF chromatin remodeling complexes and is frequently mutated in human lung adenocarcinoma. However, the functional consequences of SMARCA4 mutation on tumor initiation, progression, and chromatin regulation in lung cancer remain poorly understood. Here, we demonstrate that loss of Smarca4 sensitizes club cell secretory protein–positive cells within the lung in a cell type–dependent fashion to malignant transformation and tumor progression, resulting in highly advanced dedifferentiated tumors and increased metastatic incidence. Consistent with these phenotypes, Smarca4-deficient primary tumors lack lung lineage transcription factor activities and resemble a metastatic cell state. Mechanistically, we show that Smarca4 loss impairs the function of all three classes of SWI/SNF complexes, resulting in decreased chromatin accessibility at lung lineage motifs and ultimately accelerating tumor progression. Thus, we propose that the SWI/SNF complex via Smarca4 acts as a gatekeeper for lineage-specific cellular transformation and metastasis during lung cancer evolution. Significance: We demonstrate cell-type specificity in the tumor-suppressive functions of SMARCA4 in the lung, pointing toward a critical role of the cell-of-origin in driving SWI/SNF-mutant lung adenocarcinoma. We further show the direct effects of SMARCA4 loss on SWI/SNF function and chromatin regulation that cause aggressive malignancy during lung cancer evolution. This article is highlighted in the In This Issue feature, p. 275

Published
2022

23. BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, Concepcion, Carla P., Fahey, Caroline G., Keshishian, Hasmik, Bhutkar, Arjun, Brainson, Christine F., Sanchez-Rivera, Francisco J., Pessina, Patrizia, Kim, Jonathan Y., Simoneau, Antoine, Paschini, Margherita, Beytagh, Mary C., Stanclift, Caroline R., Schenone, Monica, Mani, D.R., Li, Chendi, Oh, Audris, Li, Fei, Hu, Hai, Karatza, Angeliki, Bronson, Roderick T., Shaw, Alice T., Hata, Aaron N., Wong, Kwok-Kin, Zou, Lee, Carr, Steven A., Jacks, Tyler, Kim, Carla F., Gupta, Manav, Concepcion, Carla P., Fahey, Caroline G., Keshishian, Hasmik, Bhutkar, Arjun, Brainson, Christine F., Sanchez-Rivera, Francisco J., Pessina, Patrizia, Kim, Jonathan Y., Simoneau, Antoine, Paschini, Margherita, Beytagh, Mary C., Stanclift, Caroline R., Schenone, Monica, Mani, D.R., Li, Chendi, Oh, Audris, Li, Fei, Hu, Hai, Karatza, Angeliki, Bronson, Roderick T., Shaw, Alice T., Hata, Aaron N., Wong, Kwok-Kin, Zou, Lee, Carr, Steven A., Jacks, Tyler, and Kim, Carla F.

Abstract

Inactivation of SMARCA4/BRG1, the core ATPase subunit of mammalian SWI/SNF complexes, occurs at very high frequencies in non-small cell lung cancers (NSCLC). There are no targeted therapies for this subset of lung cancers, nor is it known how mutations in BRG1 contribute to lung cancer progression. Using a combination of gain- and loss-of-function approaches, we demonstrate that deletion of BRG1 in lung cancer leads to activation of replication stress responses. Single-molecule assessment of replication fork dynamics in BRG1-deficient cells revealed increased origin firing mediated by the prelicensing protein, CDC6. Quantitative mass spectrometry and coimmunoprecipitation assays showed that BRG1-containing SWI/SNF complexes interact with RPA complexes. Finally, BRG1-deficient lung cancers were sensitive to pharmacologic inhibition of ATR. These findings provide novel mechanistic insight into BRG1-mutant lung cancers and suggest that their dependency on ATR can be leveraged therapeutically and potentially expanded to BRG1-mutant cancers in other tissues.

Published
2022

24. Smarca4 Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung

Author

Concepcion, Carla P., primary, Ma, Sai, additional, LaFave, Lindsay M., additional, Bhutkar, Arjun, additional, Liu, Manyuan, additional, DeAngelo, Lydia P., additional, Kim, Jonathan Y., additional, Del Priore, Isabella, additional, Schoenfeld, Adam J., additional, Miller, Manon, additional, Kartha, Vinay K., additional, Westcott, Peter M.K., additional, Sánchez-Rivera, Francisco J., additional, Meli, Kevin, additional, Gupta, Manav, additional, Bronson, Roderick T., additional, Riely, Gregory J., additional, Rekhtman, Natasha, additional, Rudin, Charles M., additional, Kim, Carla F., additional, Regev, Aviv, additional, Buenrostro, Jason D., additional, and Jacks, Tyler, additional

Published
2022
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25. BRG1 loss predisposes lung cancers to replicative stress and ATR dependency

Author

Gupta, Manav, Concepcion, Carla P, Fahey, Caroline G, Keshishian, Hasmik, Bhutkar, Arjun, Brainson, Christine F, Sanchez-Rivera, Francisco J, Pessina, Patrizia, Kim, Jonathan Y, Simoneau, Antoine, Paschini, Margherita, Beytagh, Mary C, Stanclift, Caroline R, Schenone, Monica, Mani, DR, Li, Chendi, Oh, Audris, Li, Fei, Hu, Hai, Karatza, Angeliki, Bronson, Roderick T, Shaw, Alice T, Hata, Aaron N, Wong, Kwok-Kin, Zou, Lee, Carr, Steven A, Jacks, Tyler, Kim, Carla F, Gupta, Manav, Concepcion, Carla P, Fahey, Caroline G, Keshishian, Hasmik, Bhutkar, Arjun, Brainson, Christine F, Sanchez-Rivera, Francisco J, Pessina, Patrizia, Kim, Jonathan Y, Simoneau, Antoine, Paschini, Margherita, Beytagh, Mary C, Stanclift, Caroline R, Schenone, Monica, Mani, DR, Li, Chendi, Oh, Audris, Li, Fei, Hu, Hai, Karatza, Angeliki, Bronson, Roderick T, Shaw, Alice T, Hata, Aaron N, Wong, Kwok-Kin, Zou, Lee, Carr, Steven A, Jacks, Tyler, and Kim, Carla F

Abstract

Inactivation of SMARCA4/BRG1, the core ATPase subunit of mammalian SWI/SNF complexes, occurs at very high frequencies in non-small cell lung cancers (NSCLC). There are no targeted therapies for this subset of lung cancers, nor is it known how mutations in BRG1 contribute to lung cancer progression. Using a combination of gain- and loss-of-function approaches, we demonstrate that deletion of BRG1 in lung cancer leads to activation of replication stress responses. Single-molecule assessment of replication fork dynamics in BRG1-deficient cells revealed increased origin firing mediated by the prelicensing protein, CDC6. Quantitative mass spectrometry and coimmunoprecipitation assays showed that BRG1-containing SWI/SNF complexes interact with RPA complexes. Finally, BRG1-deficient lung cancers were sensitive to pharmacologic inhibition of ATR. These findings provide novel mechanistic insight into BRG1-mutant lung cancers and suggest that their dependency on ATR can be leveraged therapeutically and potentially expanded to BRG1-mutant cancers in other tissues.

Published
2021

26. BRG1 Loss Predisposes Lung Cancers to Replicative Stress and ATR Dependency

Author

Gupta, Manav, primary, Concepcion, Carla P., additional, Fahey, Caroline G., additional, Keshishian, Hasmik, additional, Bhutkar, Arjun, additional, Brainson, Christine F., additional, Sanchez-Rivera, Francisco J., additional, Pessina, Patrizia, additional, Kim, Jonathan Y., additional, Simoneau, Antoine, additional, Paschini, Margherita, additional, Beytagh, Mary C., additional, Stanclift, Caroline R., additional, Schenone, Monica, additional, Mani, D.R., additional, Li, Chendi, additional, Oh, Audris, additional, Li, Fei, additional, Hu, Hai, additional, Karatza, Angeliki, additional, Bronson, Roderick T., additional, Shaw, Alice T., additional, Hata, Aaron N., additional, Wong, Kwok-Kin, additional, Zou, Lee, additional, Carr, Steven A., additional, Jacks, Tyler, additional, and Kim, Carla F., additional

Published
2020
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29. Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, additional, Reyes, Jaime M., additional, Li, Lewyn, additional, Rao, Prakash K., additional, Li, Fugen, additional, Lin, Charles Y., additional, Perry, Jennifer A., additional, Lawlor, Matthew A., additional, Federation, Alexander, additional, De Raedt, Thomas, additional, Li, Yvonne Y., additional, Liu, Yan, additional, Duarte, Melissa A., additional, Zhang, Yanxi, additional, Herter-Sprie, Grit S., additional, Kikuchi, Eiki, additional, Carretero, Julian, additional, Perou, Charles M., additional, Reibel, Jacob B., additional, Paulk, Joshiawa, additional, Bronson, Roderick T., additional, Watanabe, Hideo, additional, Brainson, Christine Fillmore, additional, Kim, Carla F., additional, Hammerman, Peter S., additional, Brown, Myles, additional, Cichowski, Karen, additional, Long, Henry, additional, Bradner, James E., additional, and Wong, Kwok-Kin, additional

Published
2016
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32. Requirement for Rac1 in a K-ras–Induced Lung Cancer in the Mouse

Author

Kissil, Joseph L., primary, Walmsley, Marita J., additional, Hanlon, Linda, additional, Haigis, Kevin M., additional, Bender Kim, Carla F., additional, Sweet-Cordero, Alejandro, additional, Eckman, Matthew S., additional, Tuveson, David A., additional, Capobianco, Anthony J., additional, Tybulewicz, Victor L.J., additional, and Jacks, Tyler, additional

Published
2007
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