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dc.contributor.authorGe, Rongbinen_US
dc.contributor.authorWang, Zongweien_US
dc.contributor.authorWu, Shulinen_US
dc.contributor.authorZhuo, Yangjiaen_US
dc.contributor.authorOtsetov, Aleksandar G.en_US
dc.contributor.authorCai, Chaoen_US
dc.contributor.authorZhong, Weideen_US
dc.contributor.authorWu, Chin-Leeen_US
dc.contributor.authorOlumi, Aria F.en_US
dc.date.accessioned2016-03-01T19:49:11Z
dc.date.issued2015en_US
dc.identifier.citationGe, Rongbin, Zongwei Wang, Shulin Wu, Yangjia Zhuo, Aleksandar G. Otsetov, Chao Cai, Weide Zhong, Chin-Lee Wu, and Aria F. Olumi. 2015. “Metformin represses cancer cells via alternate pathways in N-cadherin expressing vs. N-cadherin deficient cells.” Oncotarget 6 (30): 28973-28987.en
dc.identifier.issn1949-2553en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:25658381
dc.description.abstractMetformin has emerged as a potential anticancer agent. Here, we demonstrate that metformin plays an anti-tumor role via repressing N-cadherin, independent of AMPK, in wild-type N-cadherin cancer cells. Ectopic-expression of N-cadherin develops metformin-resistant cancer cells, while suppression of N-cadherin sensitizes cancer to metformin. Manipulation of AMPK expression does not alter sensitivity of cancer to metformin. We show that NF-kappaB is a downstream molecule of N-cadherin and metformin regulates NF-kappaB signaling via suppressing N-cadherin. Moreover, we also suggest that TWIST1 is an upstream molecule of N-cadherin/NF-kappaB signaling and manipulation of TWIST1 expression changes the sensitivity of cancer cells to metformin. In contrast to the cells that express N-cadherin, in N-cadherin deficient cells, metformin plays an anti-tumor role via activation of AMPK. Ectopic expression of N-cadherin makes cancer more resistant to metformin. Therefore, we suggest that metformin's anti-cancer therapeutic effect is mediated through different molecular mechanism in wild-type vs. deficient N-cadherin cancer cells. At last, we selected 49 out of 984 patients’ samples with prostatic cancer after radical prostatectomy (selection criteria: Gleason score ≥ 7 and all patients taking metformin) and showed levels of N-cadherin, p65 and AMPK could predict post-surgical recurrence in prostate cancer after treatment of metformin.en
dc.language.isoen_USen
dc.publisherImpact Journals LLCen
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745705/pdf/en
dash.licenseLAAen_US
dc.subjectprostate canceren
dc.subjectmetforminen
dc.subjectTWISTen
dc.subjectN-cadherinen
dc.titleMetformin represses cancer cells via alternate pathways in N-cadherin expressing vs. N-cadherin deficient cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalOncotargeten
dash.depositing.authorWang, Zongweien_US
dc.date.available2016-03-01T19:49:11Z
dash.authorsorderedfalse
dash.contributor.affiliatedOlumi, Aria
dash.contributor.affiliatedWu, Chin-Lee
dash.contributor.affiliatedWu, Shulin
dash.contributor.affiliatedWang, Zongwei


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