Cyclosporin A suppresses prostate cancer cell growth through CaMKK beta/AMPK-mediated inhibition of mTORC1 signaling
DC Field | Value | Language |
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dc.contributor.author | Lee, Chae Ryun | - |
dc.contributor.author | Chun, Jung Nyeo | - |
dc.contributor.author | Kim, Sang-Yeob | - |
dc.contributor.author | Park, Soonbum | - |
dc.contributor.author | Kim, Su-Hwa | - |
dc.contributor.author | Park, Eun-Jung | - |
dc.contributor.author | Kim, In-San | - |
dc.contributor.author | Cho, Nam-Hyuk | - |
dc.contributor.author | Kim, In-Gyu | - |
dc.contributor.author | So, Insuk | - |
dc.contributor.author | Kim, Tae Woo | - |
dc.contributor.author | Jeon, Ju-Hong | - |
dc.date.accessioned | 2021-09-06T16:35:11Z | - |
dc.date.available | 2021-09-06T16:35:11Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2012-08-15 | - |
dc.identifier.issn | 0006-2952 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/107701 | - |
dc.description.abstract | Cyclosporin A (CsA) has antitumor effects on various cancers including prostate cancer. However, its antitumor mechanism is poorly understood. In this study, we showed that AMP-activated protein kinase (AMPK) mediates the antitumor effect of CsA on prostate cancer cells. CsA attenuated cell growth by inducing a Cl arrest through the inhibition of mTOR complex 1 (mTORC1) signaling. In this context, Akt was paradoxically activated downstream of the EGF receptor (EGFR)-mediated increase in phosphatidylinositol 3,4,5-trisphosphate (PIP3) production. However, CsA also caused a Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKK beta)-dependent activation of AMPK, which inhibits mTORC1 signaling; this led to ineffective Akt signaling. An EGFR or Akt inhibitor increased the growth suppressive activity of CsA, whereas the combination of an AMPK inhibitor and CsA markedly rescued cells from the G1 arrest and increased cell growth. These results provide novel insights into the molecular mechanisms of CsA on cancer signaling pathways. (C) 2012 Elsevier Inc. All rights reserved. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.subject | ACTIVATED PROTEIN-KINASE | - |
dc.subject | ANDROGEN-RECEPTOR | - |
dc.subject | AMPK | - |
dc.subject | PTEN | - |
dc.subject | EXPRESSION | - |
dc.subject | PATHWAY | - |
dc.subject | PHOSPHORYLATION | - |
dc.subject | INACTIVATION | - |
dc.subject | ENDOCYTOSIS | - |
dc.subject | PROGRESSION | - |
dc.title | Cyclosporin A suppresses prostate cancer cell growth through CaMKK beta/AMPK-mediated inhibition of mTORC1 signaling | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Tae Woo | - |
dc.identifier.doi | 10.1016/j.bcp.2012.05.009 | - |
dc.identifier.scopusid | 2-s2.0-84864120335 | - |
dc.identifier.wosid | 000307135600003 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL PHARMACOLOGY, v.84, no.4, pp.425 - 431 | - |
dc.relation.isPartOf | BIOCHEMICAL PHARMACOLOGY | - |
dc.citation.title | BIOCHEMICAL PHARMACOLOGY | - |
dc.citation.volume | 84 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 425 | - |
dc.citation.endPage | 431 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | ACTIVATED PROTEIN-KINASE | - |
dc.subject.keywordPlus | ANDROGEN-RECEPTOR | - |
dc.subject.keywordPlus | AMPK | - |
dc.subject.keywordPlus | PTEN | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | INACTIVATION | - |
dc.subject.keywordPlus | ENDOCYTOSIS | - |
dc.subject.keywordPlus | PROGRESSION | - |
dc.subject.keywordAuthor | Cyclosporin A | - |
dc.subject.keywordAuthor | AMPK | - |
dc.subject.keywordAuthor | Akt | - |
dc.subject.keywordAuthor | mTOR | - |
dc.subject.keywordAuthor | Prostate cancer | - |
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