REV1 Inhibition Enhances Radioresistance and Autophagy

Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observations suggest REV1’s important role in determining ca...

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Autores principales:	Kanayo E. Ikeh, Erica N. Lamkin, Andrew Crompton, Jamie Deutsch, Kira J. Fisher, Mark Gray, David J. Argyle, Won Y. Lim, Dmitry M. Korzhnev, M. Kyle Hadden, Jiyong Hong, Pei Zhou, Nimrat Chatterjee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	translesion synthesis radioresistance autophagy REV1 ionizing radiations etoposide Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a8b30413ff89465cb626e026f8c27cf5
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id	oai:doaj.org-article:a8b30413ff89465cb626e026f8c27cf5
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spelling	oai:doaj.org-article:a8b30413ff89465cb626e026f8c27cf52021-11-11T15:27:23ZREV1 Inhibition Enhances Radioresistance and Autophagy10.3390/cancers132152902072-6694https://doaj.org/article/a8b30413ff89465cb626e026f8c27cf52021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5290https://doaj.org/toc/2072-6694Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observations suggest REV1’s important role in determining cancer cell response to chemotherapy. Whether REV1 inhibition would similarly sensitize cancer cells to radiation treatment is unknown. This study reports a lack of radiosensitization in response to REV1 inhibition by small molecule inhibitors in ionizing radiation-exposed cancer cells. Instead, REV1 inhibition unexpectedly triggers autophagy, which is a known biomarker of radioresistance. We report a possible role of the REV1 TLS protein in determining cancer treatment outcomes depending upon the type of DNA damage inflicted. Furthermore, we discover that REV1 inhibition directly triggers autophagy, an uncharacterized REV1 phenotype, with a significant bearing on cancer treatment regimens.Kanayo E. IkehErica N. LamkinAndrew CromptonJamie DeutschKira J. FisherMark GrayDavid J. ArgyleWon Y. LimDmitry M. KorzhnevM. Kyle HaddenJiyong HongPei ZhouNimrat ChatterjeeMDPI AGarticletranslesion synthesisradioresistanceautophagyREV1ionizing radiationsetoposideNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5290, p 5290 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	translesion synthesis radioresistance autophagy REV1 ionizing radiations etoposide Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	translesion synthesis radioresistance autophagy REV1 ionizing radiations etoposide Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Kanayo E. Ikeh Erica N. Lamkin Andrew Crompton Jamie Deutsch Kira J. Fisher Mark Gray David J. Argyle Won Y. Lim Dmitry M. Korzhnev M. Kyle Hadden Jiyong Hong Pei Zhou Nimrat Chatterjee REV1 Inhibition Enhances Radioresistance and Autophagy
description	Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observations suggest REV1’s important role in determining cancer cell response to chemotherapy. Whether REV1 inhibition would similarly sensitize cancer cells to radiation treatment is unknown. This study reports a lack of radiosensitization in response to REV1 inhibition by small molecule inhibitors in ionizing radiation-exposed cancer cells. Instead, REV1 inhibition unexpectedly triggers autophagy, which is a known biomarker of radioresistance. We report a possible role of the REV1 TLS protein in determining cancer treatment outcomes depending upon the type of DNA damage inflicted. Furthermore, we discover that REV1 inhibition directly triggers autophagy, an uncharacterized REV1 phenotype, with a significant bearing on cancer treatment regimens.
format	article
author	Kanayo E. Ikeh Erica N. Lamkin Andrew Crompton Jamie Deutsch Kira J. Fisher Mark Gray David J. Argyle Won Y. Lim Dmitry M. Korzhnev M. Kyle Hadden Jiyong Hong Pei Zhou Nimrat Chatterjee
author_facet	Kanayo E. Ikeh Erica N. Lamkin Andrew Crompton Jamie Deutsch Kira J. Fisher Mark Gray David J. Argyle Won Y. Lim Dmitry M. Korzhnev M. Kyle Hadden Jiyong Hong Pei Zhou Nimrat Chatterjee
author_sort	Kanayo E. Ikeh
title	REV1 Inhibition Enhances Radioresistance and Autophagy
title_short	REV1 Inhibition Enhances Radioresistance and Autophagy
title_full	REV1 Inhibition Enhances Radioresistance and Autophagy
title_fullStr	REV1 Inhibition Enhances Radioresistance and Autophagy
title_full_unstemmed	REV1 Inhibition Enhances Radioresistance and Autophagy
title_sort	rev1 inhibition enhances radioresistance and autophagy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a8b30413ff89465cb626e026f8c27cf5
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_version_	1718435259915173888

REV1 Inhibition Enhances Radioresistance and Autophagy

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