Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment

Abstract Inhibition of programmed cell death pathways is frequently observed in cancer cells where it functions to facilitate tumor progression. However, some proteins involved in the regulation of cell death function dichotomously to both promote and inhibit cell death depending on the cellular con...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Matyas Abel Tsegaye, Jianping He, Kyle McGeehan, Ireland M. Murphy, Mati Nemera, Zachary T. Schafer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d62654ece9dd4e54ab38c4da97e1c7b1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d62654ece9dd4e54ab38c4da97e1c7b1
record_format	dspace
spelling	oai:doaj.org-article:d62654ece9dd4e54ab38c4da97e1c7b12021-12-02T17:27:03ZOncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment10.1038/s41598-021-97715-42045-2322https://doaj.org/article/d62654ece9dd4e54ab38c4da97e1c7b12021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97715-4https://doaj.org/toc/2045-2322Abstract Inhibition of programmed cell death pathways is frequently observed in cancer cells where it functions to facilitate tumor progression. However, some proteins involved in the regulation of cell death function dichotomously to both promote and inhibit cell death depending on the cellular context. As such, understanding how cell death proteins are regulated in a context-dependent fashion in cancer cells is of utmost importance. We have uncovered evidence that cellular FLICE-like Inhibitory Protein (c-FLIP), a well-known anti-apoptotic protein, is often downregulated in tumor tissue when compared to adjacent normal tissue. These data argue that c-FLIP may have activity distinct from its canonical role in antagonizing cell death. Interestingly, we have discovered that detachment from extracellular matrix (ECM) serves as a signal to elevate c-FLIP transcription and that oncogenic signaling blocks ECM-detachment-induced c-FLIP elevation. In addition, our data reveal that downregulation of c-FLIP promotes luminal filling in mammary acini and that c-FLIP overexpression in cancer cells inhibits colony formation in cells exposed to ECM-detachment. Taken together, our study reveals an unexpected, non-apoptotic role for c-FLIP during ECM-detachment and raises the possibility that c-FLIP may have context-dependent roles during tumorigenesis.Matyas Abel TsegayeJianping HeKyle McGeehanIreland M. MurphyMati NemeraZachary T. SchaferNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matyas Abel Tsegaye Jianping He Kyle McGeehan Ireland M. Murphy Mati Nemera Zachary T. Schafer Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment
description	Abstract Inhibition of programmed cell death pathways is frequently observed in cancer cells where it functions to facilitate tumor progression. However, some proteins involved in the regulation of cell death function dichotomously to both promote and inhibit cell death depending on the cellular context. As such, understanding how cell death proteins are regulated in a context-dependent fashion in cancer cells is of utmost importance. We have uncovered evidence that cellular FLICE-like Inhibitory Protein (c-FLIP), a well-known anti-apoptotic protein, is often downregulated in tumor tissue when compared to adjacent normal tissue. These data argue that c-FLIP may have activity distinct from its canonical role in antagonizing cell death. Interestingly, we have discovered that detachment from extracellular matrix (ECM) serves as a signal to elevate c-FLIP transcription and that oncogenic signaling blocks ECM-detachment-induced c-FLIP elevation. In addition, our data reveal that downregulation of c-FLIP promotes luminal filling in mammary acini and that c-FLIP overexpression in cancer cells inhibits colony formation in cells exposed to ECM-detachment. Taken together, our study reveals an unexpected, non-apoptotic role for c-FLIP during ECM-detachment and raises the possibility that c-FLIP may have context-dependent roles during tumorigenesis.
format	article
author	Matyas Abel Tsegaye Jianping He Kyle McGeehan Ireland M. Murphy Mati Nemera Zachary T. Schafer
author_facet	Matyas Abel Tsegaye Jianping He Kyle McGeehan Ireland M. Murphy Mati Nemera Zachary T. Schafer
author_sort	Matyas Abel Tsegaye
title	Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment
title_short	Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment
title_full	Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment
title_fullStr	Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment
title_full_unstemmed	Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment
title_sort	oncogenic signaling inhibits c-flipl expression and its non-apoptotic function during ecm-detachment
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d62654ece9dd4e54ab38c4da97e1c7b1
work_keys_str_mv	AT matyasabeltsegaye oncogenicsignalinginhibitscfliplexpressionanditsnonapoptoticfunctionduringecmdetachment AT jianpinghe oncogenicsignalinginhibitscfliplexpressionanditsnonapoptoticfunctionduringecmdetachment AT kylemcgeehan oncogenicsignalinginhibitscfliplexpressionanditsnonapoptoticfunctionduringecmdetachment AT irelandmmurphy oncogenicsignalinginhibitscfliplexpressionanditsnonapoptoticfunctionduringecmdetachment AT matinemera oncogenicsignalinginhibitscfliplexpressionanditsnonapoptoticfunctionduringecmdetachment AT zacharytschafer oncogenicsignalinginhibitscfliplexpressionanditsnonapoptoticfunctionduringecmdetachment
_version_	1718380817141465088

Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment

Ejemplares similares