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

Simple item page
dc.creatorBasu, Alakananda
dc.creator.orcid0000-0002-1656-0788 (Basu, Alakananda)
dc.date.accessioned2022-08-22T18:10:30Z
dc.date.available2022-08-22T18:10:30Z
dc.date.issued2020-06-15
dc.description.abstractProtein 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.
dc.description.sponsorshipThis research received no external funding.
dc.identifier.citationBasu 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/ijms21124247
dc.identifier.issn1422-0067
dc.identifier.issue12
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31600
dc.identifier.volume21
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/ijms21124247
dc.rights.holder© 2020 by the author.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceInternational Journal of Molecular Sciences
dc.subjectapoptosis
dc.subjectautophagy
dc.subjectbreast cancer
dc.subjectmTORC1
dc.subjectmTORC2
dc.subject.meshAutophagy / drug effects
dc.subject.meshBreast Neoplasms / genetics
dc.subject.meshBreast Neoplasms / metabolism
dc.subject.meshCell Line, Tumor
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation, Neoplastic / drug effects
dc.subject.meshGene Silencing
dc.subject.meshHumans
dc.subject.meshMCF-7 Cells
dc.subject.meshMacrolides / pharmacology
dc.subject.meshMechanistic Target of Rapamycin Complex 1 / metabolism
dc.subject.meshMicrotubule-Associated Proteins / metabolism
dc.subject.meshProtein Kinase C-epsilon / genetics
dc.subject.meshProtein Kinase C-epsilon / metabolism
dc.subject.meshRNA, Small Interfering / pharmacology
dc.subject.meshSequestosome-1 Protein / metabolism
dc.titleRegulation of Autophagy by Protein Kinase C-epsilon in Breast Cancer Cells
dc.typeArticle
dc.type.materialtext

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
10.3390_ijms21124247.pdf
Size:
3.15 MB
Format:
Adobe Portable Document Format
Description:
full text article
Download

Collections

Publications -- Alakananda Basu