Attribution 4.0 International (CC BY 4.0)2022-08-222022-08-222020-06-15Basu A. (2020). Regulation of Autophagy by Protein Kinase C-ɛ in Breast Cancer Cells. International journal of molecular sciences, 21(12), 4247. https://doi.org/10.3390/ijms211242471422-0067https://hdl.handle.net/20.500.12503/31600Protein kinase C-ɛ (PKCɛ), 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 PKCɛ regulates autophagy in breast cancer cells. We have shown that silencing of PKCɛ 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 PKCɛ attenuated an increase in autophagy caused by the depletion of Raptor and Rictor. Overexpression of PKCɛ 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 PKCɛ overexpressing cells. While overexpression of PKCɛ in MCF-7 cells inhibited apoptosis, it induced autophagy in response to tumor necrosis factor-ɑ. However, inhibition of autophagy by Atg5 knockdown restored apoptosis in PKCɛ-overexpressing cells. Thus, PKCɛ promotes breast cancer cell survival not only by inhibiting apoptosis but also by inducing autophagy.http://creativecommons.org/licenses/by/4.0/apoptosisautophagybreast cancermTORC1mTORC2Autophagy / drug effectsBreast Neoplasms / geneticsBreast Neoplasms / metabolismCell Line, TumorFemaleGene Expression Regulation, Neoplastic / drug effectsGene SilencingHumansMCF-7 CellsMacrolides / pharmacologyMechanistic Target of Rapamycin Complex 1 / metabolismMicrotubule-Associated Proteins / metabolismProtein Kinase C-epsilon / geneticsProtein Kinase C-epsilon / metabolismRNA, Small Interfering / pharmacologySequestosome-1 Protein / metabolismArticle© 2020 by the author.2112