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PKCeta Promotes Stress-Induced Autophagy and Senescence in Breast Cancer Cells, Presenting a Target for Therapy

The emergence of chemoresistance in neoplastic cells is one of the major obstacles in cancer therapy. Autophagy was recently reported as one of the mechanisms that promote chemoresistance in cancer cells by protecting against apoptosis and driving senescence. Thus, understanding the role of autophag...

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Autores principales: Rotem-Dai, Noa, Muraleedharan, Amitha, Livneh, Etta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413313/
https://www.ncbi.nlm.nih.gov/pubmed/36015330
http://dx.doi.org/10.3390/pharmaceutics14081704
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author Rotem-Dai, Noa
Muraleedharan, Amitha
Livneh, Etta
author_facet Rotem-Dai, Noa
Muraleedharan, Amitha
Livneh, Etta
author_sort Rotem-Dai, Noa
collection PubMed
description The emergence of chemoresistance in neoplastic cells is one of the major obstacles in cancer therapy. Autophagy was recently reported as one of the mechanisms that promote chemoresistance in cancer cells by protecting against apoptosis and driving senescence. Thus, understanding the role of autophagy and its underlying signaling pathways is crucial for the development of new therapeutic strategies to overcome chemoresistance. We have previously reported that PKCη is a stress-induced kinase that confers resistance in breast cancer cells against chemotherapy by inducing senescence. Here, we show that PKCη promotes autophagy induced by ER and oxidative stress and facilitates the transition from autophagy to senescence. We demonstrate that PKCη knockdown reduces both the autophagic flux and markers of senescence. Additionally, using autophagy inhibitors such as chloroquine and 3-methyladenine, we show that PKCη and autophagy are required for establishing senescence in MCF-7 in response to oxidative stress. Different drugs used in the clinic are known to induce autophagy and senescence in breast cancer cells. Our study proposes PKCη as a target for therapeutic intervention, acting in synergy with autophagy-inducing drugs to overcome resistance and enhance cell death in breast cancer.
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spelling pubmed-94133132022-08-27 PKCeta Promotes Stress-Induced Autophagy and Senescence in Breast Cancer Cells, Presenting a Target for Therapy Rotem-Dai, Noa Muraleedharan, Amitha Livneh, Etta Pharmaceutics Brief Report The emergence of chemoresistance in neoplastic cells is one of the major obstacles in cancer therapy. Autophagy was recently reported as one of the mechanisms that promote chemoresistance in cancer cells by protecting against apoptosis and driving senescence. Thus, understanding the role of autophagy and its underlying signaling pathways is crucial for the development of new therapeutic strategies to overcome chemoresistance. We have previously reported that PKCη is a stress-induced kinase that confers resistance in breast cancer cells against chemotherapy by inducing senescence. Here, we show that PKCη promotes autophagy induced by ER and oxidative stress and facilitates the transition from autophagy to senescence. We demonstrate that PKCη knockdown reduces both the autophagic flux and markers of senescence. Additionally, using autophagy inhibitors such as chloroquine and 3-methyladenine, we show that PKCη and autophagy are required for establishing senescence in MCF-7 in response to oxidative stress. Different drugs used in the clinic are known to induce autophagy and senescence in breast cancer cells. Our study proposes PKCη as a target for therapeutic intervention, acting in synergy with autophagy-inducing drugs to overcome resistance and enhance cell death in breast cancer. MDPI 2022-08-16 /pmc/articles/PMC9413313/ /pubmed/36015330 http://dx.doi.org/10.3390/pharmaceutics14081704 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Rotem-Dai, Noa
Muraleedharan, Amitha
Livneh, Etta
PKCeta Promotes Stress-Induced Autophagy and Senescence in Breast Cancer Cells, Presenting a Target for Therapy
title PKCeta Promotes Stress-Induced Autophagy and Senescence in Breast Cancer Cells, Presenting a Target for Therapy
title_full PKCeta Promotes Stress-Induced Autophagy and Senescence in Breast Cancer Cells, Presenting a Target for Therapy
title_fullStr PKCeta Promotes Stress-Induced Autophagy and Senescence in Breast Cancer Cells, Presenting a Target for Therapy
title_full_unstemmed PKCeta Promotes Stress-Induced Autophagy and Senescence in Breast Cancer Cells, Presenting a Target for Therapy
title_short PKCeta Promotes Stress-Induced Autophagy and Senescence in Breast Cancer Cells, Presenting a Target for Therapy
title_sort pkceta promotes stress-induced autophagy and senescence in breast cancer cells, presenting a target for therapy
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413313/
https://www.ncbi.nlm.nih.gov/pubmed/36015330
http://dx.doi.org/10.3390/pharmaceutics14081704
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