Molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment

Abstract During cancer, a major challenge faced by oncologists is the treatment of metastasis; a leading cause of cancer-related deaths around the world. Metastasis involves a highly ordered sequence of events starting with the detachment of tumor cells from the extracellular matrix (E.C.M.). In nor...

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Autores principales:	Mohammad Imran Khan, Mazin A. Zamzami, Aftab Ahmad, Hani Choudhry
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d0e91a9b0dc749debab2535c38277a45
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spelling	oai:doaj.org-article:d0e91a9b0dc749debab2535c38277a452021-12-02T14:06:18ZMolecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment10.1038/s41598-021-82431-w2045-2322https://doaj.org/article/d0e91a9b0dc749debab2535c38277a452021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82431-whttps://doaj.org/toc/2045-2322Abstract During cancer, a major challenge faced by oncologists is the treatment of metastasis; a leading cause of cancer-related deaths around the world. Metastasis involves a highly ordered sequence of events starting with the detachment of tumor cells from the extracellular matrix (E.C.M.). In normal cells, detachment from E.C.M. triggers programmed cell death, termed anoikis. However, tumor cells dodge their way to anoikis and spread to distant sites for initiating the metastatic program. In this work, we explored the impact of E.C.M. detachment on the expression of some major oncogenic histone methyltransferases. Results showed both EZH2 expression and its enzymatic activity were significantly increased in E.C.M. detached cancer cells when compared to the attached cells. Inhibition of EZH2 results in a significant reduction in cell proliferation, spheroids size, and induction in apoptosis in E.C.M. detached cells. Furthermore, we observed a reduction in EZH2 expression levels in single cells when compared to clusters of E.C.M. detached cells. Finally, we combined the EZH2 inhibition with AMPK, known to be highly expressed in E.C.M. detached cancer cells and observed antagonistic effects between the two pathways. The observed results clearly showed that E.C.M. detached cancer cells require oncogenic EZH2 and can be targeted by EZH2 inhibitors.Mohammad Imran KhanMazin A. ZamzamiAftab AhmadHani ChoudhryNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohammad Imran Khan Mazin A. Zamzami Aftab Ahmad Hani Choudhry Molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment
description	Abstract During cancer, a major challenge faced by oncologists is the treatment of metastasis; a leading cause of cancer-related deaths around the world. Metastasis involves a highly ordered sequence of events starting with the detachment of tumor cells from the extracellular matrix (E.C.M.). In normal cells, detachment from E.C.M. triggers programmed cell death, termed anoikis. However, tumor cells dodge their way to anoikis and spread to distant sites for initiating the metastatic program. In this work, we explored the impact of E.C.M. detachment on the expression of some major oncogenic histone methyltransferases. Results showed both EZH2 expression and its enzymatic activity were significantly increased in E.C.M. detached cancer cells when compared to the attached cells. Inhibition of EZH2 results in a significant reduction in cell proliferation, spheroids size, and induction in apoptosis in E.C.M. detached cells. Furthermore, we observed a reduction in EZH2 expression levels in single cells when compared to clusters of E.C.M. detached cells. Finally, we combined the EZH2 inhibition with AMPK, known to be highly expressed in E.C.M. detached cancer cells and observed antagonistic effects between the two pathways. The observed results clearly showed that E.C.M. detached cancer cells require oncogenic EZH2 and can be targeted by EZH2 inhibitors.
format	article
author	Mohammad Imran Khan Mazin A. Zamzami Aftab Ahmad Hani Choudhry
author_facet	Mohammad Imran Khan Mazin A. Zamzami Aftab Ahmad Hani Choudhry
author_sort	Mohammad Imran Khan
title	Molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment
title_short	Molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment
title_full	Molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment
title_fullStr	Molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment
title_full_unstemmed	Molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment
title_sort	molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d0e91a9b0dc749debab2535c38277a45
work_keys_str_mv	AT mohammadimrankhan molecularprofilingofepigeneticlandscapeofcancercellsduringextracellularmatrixdetachment AT mazinazamzami molecularprofilingofepigeneticlandscapeofcancercellsduringextracellularmatrixdetachment AT aftabahmad molecularprofilingofepigeneticlandscapeofcancercellsduringextracellularmatrixdetachment AT hanichoudhry molecularprofilingofepigeneticlandscapeofcancercellsduringextracellularmatrixdetachment
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Molecular profiling of epigenetic landscape of cancer cells during extracellular matrix detachment

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