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241 results on '"O'Hagan, Heather M."'

7. PTEN depletion reduces H3K27me3 levels to promote epithelial-to-mesenchymal transition in epithelial colorectal cancer cells.

Author

Ghobashi, Ahmed H., Kimani, Jane W., Ladaika, Christopher A., and O'Hagan, Heather M.

Subjects
AP-1 transcription factor, PTEN protein, TRANSCRIPTION factors, EPITHELIAL-mesenchymal transition, COLORECTAL cancer
Abstract

Epithelial-to-mesenchymal (EMT) transition is one of the best-known examples of tumor cell plasticity. EMT enhances cancer cell metastasis, which is the main cause of colorectal cancer (CRC)-related mortality. Therefore, understanding underlying molecular mechanisms contributing to the EMT process is crucial to finding druggable targets and more effective therapeutic approaches in CRC. In this study, we demonstrated that phosphatase and tensin homolog (PTEN) knockdown (KD) induces EMT in epithelial CRC, likely through the activation of AKT. PTEN KD modulated chromatin accessibility and reprogrammed gene transcription to mediate EMT in epithelial CRC cells. Active AKT can phosphorylate enhancer of zeste homolog 2 (EZH2) on serine 21, which switches EZH2 from a transcriptional repressor to an activator. Interestingly, PTEN KD reduced the global levels of trimethylation of histone 3 at lysine 27(H3K27me3) in an EZH2-phosphorylation-dependent manner. Additionally, EZH2 phosphorylation at serine 21 reduced the interaction of EZH2 with another polycomb repressive complex 2 (PRC2) component, suppressor of zeste 12 (SUZ12), suggesting that the reduced H3K27me3 levels in PTEN KD cells were due to a disruption of the PRC2 complex. Overall, we demonstrated that PTEN KD modulates changes in gene expression to induce the EMT process in epithelial CRC cells by phosphorylating EZH2 and activates transcription factors such as activator protein 1 (AP1). [ABSTRACT FROM AUTHOR]

Published
2024
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18. Supplementary Materials and Methods from Lysine-Specific Demethylase 1 Mediates AKT Activity and Promotes Epithelial-to-Mesenchymal Transition in PIK3CA-Mutant Colorectal Cancer

Author

Miller, Samuel A., primary, Policastro, Robert A., primary, Savant, Sudha S., primary, Sriramkumar, Shruthi, primary, Ding, Ning, primary, Lu, Xiaoyu, primary, Mohammad, Helai P., primary, Cao, Sha, primary, Kalin, Jay H., primary, Cole, Philip A., primary, Zentner, Gabriel E., primary, and O'Hagan, Heather M., primary

Published
2023
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19. Supplementary Table S5 from Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy

Author

DeStefano Shields, Christina E., primary, White, James R., primary, Chung, Liam, primary, Wenzel, Alyssa, primary, Hicks, Jessica L., primary, Tam, Ada J., primary, Chan, June L., primary, Dejea, Christine M., primary, Fan, Hongni, primary, Michel, John, primary, Maiuri, Ashley R., primary, Sriramkumar, Shruthi, primary, Podicheti, Ram, primary, Rusch, Douglas B., primary, Wang, Hao, primary, De Marzo, Angelo M., primary, Besharati, Sepideh, primary, Anders, Robert A., primary, Baylin, Stephen B., primary, O'Hagan, Heather M., primary, Housseau, Franck, primary, and Sears, Cynthia L., primary

Published
2023
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20. Supplementary Figures 1-7 and Table S1 from Lysine-Specific Demethylase 1 Mediates AKT Activity and Promotes Epithelial-to-Mesenchymal Transition in PIK3CA-Mutant Colorectal Cancer

Author

Miller, Samuel A., primary, Policastro, Robert A., primary, Savant, Sudha S., primary, Sriramkumar, Shruthi, primary, Ding, Ning, primary, Lu, Xiaoyu, primary, Mohammad, Helai P., primary, Cao, Sha, primary, Kalin, Jay H., primary, Cole, Philip A., primary, Zentner, Gabriel E., primary, and O'Hagan, Heather M., primary

Published
2023
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22. Data from Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy

Author

DeStefano Shields, Christina E., primary, White, James R., primary, Chung, Liam, primary, Wenzel, Alyssa, primary, Hicks, Jessica L., primary, Tam, Ada J., primary, Chan, June L., primary, Dejea, Christine M., primary, Fan, Hongni, primary, Michel, John, primary, Maiuri, Ashley R., primary, Sriramkumar, Shruthi, primary, Podicheti, Ram, primary, Rusch, Douglas B., primary, Wang, Hao, primary, De Marzo, Angelo M., primary, Besharati, Sepideh, primary, Anders, Robert A., primary, Baylin, Stephen B., primary, O'Hagan, Heather M., primary, Housseau, Franck, primary, and Sears, Cynthia L., primary

Published
2023
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23. Supplementary Figures S1-S6, Table S4, Table S6 from Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy

Author

DeStefano Shields, Christina E., primary, White, James R., primary, Chung, Liam, primary, Wenzel, Alyssa, primary, Hicks, Jessica L., primary, Tam, Ada J., primary, Chan, June L., primary, Dejea, Christine M., primary, Fan, Hongni, primary, Michel, John, primary, Maiuri, Ashley R., primary, Sriramkumar, Shruthi, primary, Podicheti, Ram, primary, Rusch, Douglas B., primary, Wang, Hao, primary, De Marzo, Angelo M., primary, Besharati, Sepideh, primary, Anders, Robert A., primary, Baylin, Stephen B., primary, O'Hagan, Heather M., primary, Housseau, Franck, primary, and Sears, Cynthia L., primary

Published
2023
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24. Data from Lysine-Specific Demethylase 1 Mediates AKT Activity and Promotes Epithelial-to-Mesenchymal Transition in PIK3CA-Mutant Colorectal Cancer

Author

Miller, Samuel A., primary, Policastro, Robert A., primary, Savant, Sudha S., primary, Sriramkumar, Shruthi, primary, Ding, Ning, primary, Lu, Xiaoyu, primary, Mohammad, Helai P., primary, Cao, Sha, primary, Kalin, Jay H., primary, Cole, Philip A., primary, Zentner, Gabriel E., primary, and O'Hagan, Heather M., primary

Published
2023
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26. Supplementary Tables 1-3 from Frequent Inactivation of Cysteine Dioxygenase Type 1 Contributes to Survival of Breast Cancer Cells and Resistance to Anthracyclines

Author

Jeschke, Jana, primary, O'Hagan, Heather M., primary, Zhang, Wei, primary, Vatapalli, Rajita, primary, Calmon, Marilia Freitas, primary, Danilova, Ludmila, primary, Nelkenbrecher, Claudia, primary, Van Neste, Leander, primary, Bijsmans, Ingrid T.G.W., primary, Van Engeland, Manon, primary, Gabrielson, Edward, primary, Schuebel, Kornel E., primary, Winterpacht, Andreas, primary, Baylin, Stephen B., primary, Herman, James G., primary, and Ahuja, Nita, primary

Published
2023
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33. Supplementary Figures 1-3 from Frequent Inactivation of Cysteine Dioxygenase Type 1 Contributes to Survival of Breast Cancer Cells and Resistance to Anthracyclines

Author

Jeschke, Jana, primary, O'Hagan, Heather M., primary, Zhang, Wei, primary, Vatapalli, Rajita, primary, Calmon, Marilia Freitas, primary, Danilova, Ludmila, primary, Nelkenbrecher, Claudia, primary, Van Neste, Leander, primary, Bijsmans, Ingrid T.G.W., primary, Van Engeland, Manon, primary, Gabrielson, Edward, primary, Schuebel, Kornel E., primary, Winterpacht, Andreas, primary, Baylin, Stephen B., primary, Herman, James G., primary, and Ahuja, Nita, primary

Published
2023
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47. Colon Tumors in Enterotoxigenic Bacteroides fragilis (ETBF)-Colonized Mice Do Not Display a Unique Mutational Signature but Instead Possess Host-Dependent Alterations in the APC Gene

Author

Allen, Jawara, primary, Rosendahl Huber, Axel, additional, Pleguezuelos-Manzano, Cayetano, additional, Puschhof, Jens, additional, Wu, Shaoguang, additional, Wu, Xinqun, additional, Boot, Charelle, additional, Saftien, Aurelia, additional, O’Hagan, Heather M., additional, Wang, Hao, additional, van Boxtel, Ruben, additional, Clevers, Hans, additional, and Sears, Cynthia L., additional

Published
2022
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48. Colon Tumors in Enterotoxigenic Bacteroides fragilis (ETBF)-Colonized Mice Do Not Display a Unique Mutational Signature but Instead Possess Host-Dependent Alterations in the APC Gene

Author

Allen, Jawara, Rosendahl Huber, Axel, Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Wu, Shaoguang, Wu, Xinqun, Boot, Charelle, Saftien, Aurelia, O'Hagan, Heather M, Wang, Hao, van Boxtel, Ruben, Clevers, Hans, Sears, Cynthia L, Allen, Jawara, Rosendahl Huber, Axel, Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Wu, Shaoguang, Wu, Xinqun, Boot, Charelle, Saftien, Aurelia, O'Hagan, Heather M, Wang, Hao, van Boxtel, Ruben, Clevers, Hans, and Sears, Cynthia L

Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) is consistently found at higher frequency in individuals with sporadic and hereditary colorectal cancer (CRC) and induces tumorigenesis in several mouse models of CRC. However, whether specific mutations induced by ETBF lead to colon tumor formation has not been investigated. To determine if ETBF-induced mutations impact the Apc gene, and other tumor suppressors or proto-oncogenes, we performed whole-exome sequencing and whole-genome sequencing on tumors isolated after ETBF and sham colonization of Apcmin/+ and Apcmin/+Msh2fl/flVC mice, as well as whole-genome sequencing of organoids cocultured with ETBF. Our results indicate that ETBF-induced tumor formation results from loss of heterozygosity (LOH) of Apc, unless the mismatch repair system is disrupted, in which case, tumor formation results from new acquisition of protein-truncating mutations in Apc. In contrast to polyketide synthase-positive Escherichia coli (pks+ E. coli), ETBF does not produce a unique mutational signature; instead, ETBF-induced tumors arise from errors in DNA mismatch repair and homologous recombination DNA damage repair, established pathways of tumor formation in the colon, and the same genetic mechanism accounting for sham tumors in these mouse models. Our analysis informs how this procarcinogenic bacterium may promote tumor formation in individuals with inherited predispositions to CRC, such as Lynch syndrome or familial adenomatous polyposis (FAP). IMPORTANCE Many studies have shown that microbiome composition in both the mucosa and the stool differs in individuals with sporadic and hereditary colorectal cancer (CRC). Both human and mouse models have established a strong association between particular microbes and colon tumor induction. However, the genetic mechanisms underlying putative microbe-induced colon tumor formation are not well established. In this paper, we applied whole-exome sequencing and whole-genome sequencing to investigate

Published
2022

49. Colon Tumors in Enterotoxigenic Bacteroides fragilis (ETBF)Colonized Mice Do Not Display a Unique Mutational Signature but Instead Possess Host-Dependent Alterations in the APC Gene

Author

CMM, Cancer, Hubrecht Institute with UMC, Allen, Jawara, Huber, Axel Rosendahl, Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Wu, Shaoguang, Wu, Xinqun, Boot, Charelle, Saftien, Aurelia, O’Hagan, Heather M., Wang, Hao, van Boxtel, Ruben, Clevers, Hans, Sears, Cynthia L., CMM, Cancer, Hubrecht Institute with UMC, Allen, Jawara, Huber, Axel Rosendahl, Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Wu, Shaoguang, Wu, Xinqun, Boot, Charelle, Saftien, Aurelia, O’Hagan, Heather M., Wang, Hao, van Boxtel, Ruben, Clevers, Hans, and Sears, Cynthia L.

Published
2022

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