Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells.
Identifieur interne : 000059 ( Main/Exploration ); précédent : 000058; suivant : 000060Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells.
Auteurs : Alakananda Basu [États-Unis]Source :
- International journal of molecular sciences [ 1422-0067 ] ; 2020.
Abstract
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.
DOI: 10.3390/ijms21124247
PubMed: 32549199
PubMed Central: PMC7352677
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells.</title><author><name sortKey="Basu, Alakananda" sort="Basu, Alakananda" uniqKey="Basu A" first="Alakananda" last="Basu">Alakananda Basu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32549199</idno><idno type="pmid">32549199</idno><idno type="doi">10.3390/ijms21124247</idno><idno type="pmc">PMC7352677</idno><idno type="wicri:Area/Main/Corpus">000060</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000060</idno><idno type="wicri:Area/Main/Curation">000060</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000060</idno><idno type="wicri:Area/Main/Exploration">000060</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells.</title><author><name sortKey="Basu, Alakananda" sort="Basu, Alakananda" uniqKey="Basu A" first="Alakananda" last="Basu">Alakananda Basu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author></analytic><series><title level="j">International journal of molecular sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32549199</PMID><DateRevised><Year>2020</Year><Month>07</Month><Day>22</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1422-0067</ISSN><JournalIssue CitedMedium="Internet"><Volume>21</Volume><Issue>12</Issue><PubDate><Year>2020</Year><Month>Jun</Month><Day>15</Day></PubDate></JournalIssue><Title>International journal of molecular sciences</Title><ISOAbbreviation>Int J Mol Sci</ISOAbbreviation></Journal><ArticleTitle>Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">E4247</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/ijms21124247</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Basu</LastName><ForeName>Alakananda</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0002-1656-0788</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>06</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Int J Mol Sci</MedlineTA><NlmUniqueID>101092791</NlmUniqueID><ISSNLinking>1422-0067</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">PKCε</Keyword><Keyword MajorTopicYN="N">Raptor</Keyword><Keyword MajorTopicYN="N">Rictor</Keyword><Keyword MajorTopicYN="N">apoptosis</Keyword><Keyword MajorTopicYN="N">autophagy</Keyword><Keyword MajorTopicYN="N">breast cancer</Keyword><Keyword MajorTopicYN="N">mTORC1</Keyword><Keyword MajorTopicYN="N">mTORC2</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>05</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>06</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>06</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>6</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>6</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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