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Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells

Protein kinase C-ε (PKCε), an anti-apoptotic protein, plays critical roles in breast cancer development and progression. Although autophagy is an important survival mechanism, it is not known if PKCε regulates autophagy in breast cancer cells. We have shown that silencing of PKCε by siRNA inhibited...

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Autor principal: Basu, Alakananda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352677/
https://www.ncbi.nlm.nih.gov/pubmed/32549199
http://dx.doi.org/10.3390/ijms21124247
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author Basu, Alakananda
author_facet Basu, Alakananda
author_sort Basu, Alakananda
collection PubMed
description Protein kinase C-ε (PKCε), an anti-apoptotic protein, plays critical roles in breast cancer development and progression. Although autophagy is an important survival mechanism, it is not known if PKCε regulates autophagy in breast cancer cells. We have shown that silencing of PKCε by siRNA inhibited basal and starvation-induced autophagy in T47D breast cancer cells as determined by the decrease in LC3-II, increase in p62, and decrease in autophagy puncta both in the presence and absence of bafilomycin A1. The mechanistic target of rapamycin (mTOR) associates with Raptor or Rictor to form complex-1 (mTORC1) or complex-2 (mTORC2), respectively. Knockdown of PKCε attenuated an increase in autophagy caused by the depletion of Raptor and Rictor. Overexpression of PKCε in MCF-7 cells caused activation of mTORC1 and an increase in LC3-I, LC3-II, and p62. The mTORC1 inhibitor rapamycin abolished the increase in LC3-I and p62. Knockdown of mTOR and Rictor or starvation enhanced autophagy in PKCε overexpressing cells. While overexpression of PKCε in MCF-7 cells inhibited apoptosis, it induced autophagy in response to tumor necrosis factor-α. However, inhibition of autophagy by Atg5 knockdown restored apoptosis in PKCε-overexpressing cells. Thus, PKCε promotes breast cancer cell survival not only by inhibiting apoptosis but also by inducing autophagy.
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spelling pubmed-73526772020-07-21 Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells Basu, Alakananda Int J Mol Sci Article Protein kinase C-ε (PKCε), an anti-apoptotic protein, plays critical roles in breast cancer development and progression. Although autophagy is an important survival mechanism, it is not known if PKCε regulates autophagy in breast cancer cells. We have shown that silencing of PKCε by siRNA inhibited basal and starvation-induced autophagy in T47D breast cancer cells as determined by the decrease in LC3-II, increase in p62, and decrease in autophagy puncta both in the presence and absence of bafilomycin A1. The mechanistic target of rapamycin (mTOR) associates with Raptor or Rictor to form complex-1 (mTORC1) or complex-2 (mTORC2), respectively. Knockdown of PKCε attenuated an increase in autophagy caused by the depletion of Raptor and Rictor. Overexpression of PKCε in MCF-7 cells caused activation of mTORC1 and an increase in LC3-I, LC3-II, and p62. The mTORC1 inhibitor rapamycin abolished the increase in LC3-I and p62. Knockdown of mTOR and Rictor or starvation enhanced autophagy in PKCε overexpressing cells. While overexpression of PKCε in MCF-7 cells inhibited apoptosis, it induced autophagy in response to tumor necrosis factor-α. However, inhibition of autophagy by Atg5 knockdown restored apoptosis in PKCε-overexpressing cells. Thus, PKCε promotes breast cancer cell survival not only by inhibiting apoptosis but also by inducing autophagy. MDPI 2020-06-15 /pmc/articles/PMC7352677/ /pubmed/32549199 http://dx.doi.org/10.3390/ijms21124247 Text en © 2020 by the author. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Basu, Alakananda
Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells
title Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells
title_full Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells
title_fullStr Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells
title_full_unstemmed Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells
title_short Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells
title_sort regulation of autophagy by protein kinase c-ε in breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352677/
https://www.ncbi.nlm.nih.gov/pubmed/32549199
http://dx.doi.org/10.3390/ijms21124247
work_keys_str_mv AT basualakananda regulationofautophagybyproteinkinaseceinbreastcancercells