{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:10Z","timestamp":1787028430316,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Protein kinase C-\u03b5 (PKC\u03b5), 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 PKC\u03b5 regulates autophagy in breast cancer cells. We have shown that silencing of PKC\u03b5 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 PKC\u03b5 attenuated an increase in autophagy caused by the depletion of Raptor and Rictor. Overexpression of PKC\u03b5 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 PKC\u03b5 overexpressing cells. While overexpression of PKC\u03b5 in MCF-7 cells inhibited apoptosis, it induced autophagy in response to tumor necrosis factor-\u03b1. However, inhibition of autophagy by Atg5 knockdown restored apoptosis in PKC\u03b5-overexpressing cells. Thus, PKC\u03b5 promotes breast cancer cell survival not only by inhibiting apoptosis but also by inducing autophagy.<\/jats:p>","DOI":"10.3390\/ijms21124247","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T05:56:27Z","timestamp":1592200587000},"page":"4247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Regulation of Autophagy by Protein Kinase C-\u03b5 in Breast Cancer Cells"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1656-0788","authenticated-orcid":false,"given":"Alakananda","family":"Basu","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/308693a0","article-title":"The role of protein kinase C in cell surface signal transduction and tumour promotion","volume":"308","author":"Nishizuka","year":"1984","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0163-7258(93)90070-T","article-title":"The potential of protein kinase C as a target for anticancer treatment","volume":"59","author":"Basu","year":"1993","journal-title":"Pharmacol. 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