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Article: Adiponectin promotes pancreatic cancer progression by inhibiting apoptosis via the activation of AMPK/Sirt1/PGC-1α signaling

TitleAdiponectin promotes pancreatic cancer progression by inhibiting apoptosis via the activation of AMPK/Sirt1/PGC-1α signaling
Authors
Issue Date2014
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2014, v. 5 n. 13, p. 4732-4745 How to Cite?
AbstractAdiponectin is an adipocyte-secreted adipokine with pleiotropic actions. Clinical evidence has shown that serum adiponectin levels are increased and that adiponectin can protect pancreatic beta cells against apoptosis, which suggests that adiponectin may play an anti-apoptotic role in pancreatic cancer (PC). Here, we investigated the effects of adiponectin on PC development and elucidated the underlying molecular mechanisms. Adiponectin deficiency markedly attenuated pancreatic tumorigenesis in vivo. We found that adiponectin significantly inhibited the apoptosis of both human and mouse pancreatic cancer cells via adipoR1, but not adipoR2. Furthermore, adiponectin can increase AMP-activated protein kinase (AMPK) phosphorylation and NAD-dependent deacetylase sirtuin-1 (Sirt1) of PC cells. Knockdown of AMPK or Sirt1 can increase the apoptosis in PC cells. AMPK up-regulated Sirt1, and Sirt1 can inversely phosphorylate AMPK. Further studies have shown that Sirt1 can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which can increase the expression levels of mitochondrial genes. Thus, adiponectin exerts potent anti-apoptotic effects on PC cells via the activation of AMPK/Sirt1/PGC1α signaling. Finally, adiponectin can elevate β-catenin levels. Taken together, these novel findings reveal an unconventional role of adiponectin in promoting pancreatic cancers, and suggest that the effects of adiponectin on tumorigenesis are highly tissue-dependent.
Persistent Identifierhttp://hdl.handle.net/10722/214314
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorHuang, B-
dc.contributor.authorCheng, X-
dc.contributor.authorWang, D-
dc.contributor.authorPeng, M-
dc.contributor.authorXue, Z-
dc.contributor.authorDa, Y-
dc.contributor.authorZhang, N-
dc.contributor.authorYao, Z-
dc.contributor.authorLi, M-
dc.contributor.authorXu, A-
dc.contributor.authorZhang, R-
dc.date.accessioned2015-08-21T11:12:23Z-
dc.date.available2015-08-21T11:12:23Z-
dc.date.issued2014-
dc.identifier.citationOncotarget, 2014, v. 5 n. 13, p. 4732-4745-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/214314-
dc.description.abstractAdiponectin is an adipocyte-secreted adipokine with pleiotropic actions. Clinical evidence has shown that serum adiponectin levels are increased and that adiponectin can protect pancreatic beta cells against apoptosis, which suggests that adiponectin may play an anti-apoptotic role in pancreatic cancer (PC). Here, we investigated the effects of adiponectin on PC development and elucidated the underlying molecular mechanisms. Adiponectin deficiency markedly attenuated pancreatic tumorigenesis in vivo. We found that adiponectin significantly inhibited the apoptosis of both human and mouse pancreatic cancer cells via adipoR1, but not adipoR2. Furthermore, adiponectin can increase AMP-activated protein kinase (AMPK) phosphorylation and NAD-dependent deacetylase sirtuin-1 (Sirt1) of PC cells. Knockdown of AMPK or Sirt1 can increase the apoptosis in PC cells. AMPK up-regulated Sirt1, and Sirt1 can inversely phosphorylate AMPK. Further studies have shown that Sirt1 can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which can increase the expression levels of mitochondrial genes. Thus, adiponectin exerts potent anti-apoptotic effects on PC cells via the activation of AMPK/Sirt1/PGC1α signaling. Finally, adiponectin can elevate β-catenin levels. Taken together, these novel findings reveal an unconventional role of adiponectin in promoting pancreatic cancers, and suggest that the effects of adiponectin on tumorigenesis are highly tissue-dependent.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleAdiponectin promotes pancreatic cancer progression by inhibiting apoptosis via the activation of AMPK/Sirt1/PGC-1α signaling-
dc.typeArticle-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturepublished_or_final_version-
dc.identifier.pmid25051362-
dc.identifier.pmcidPMC4148095-
dc.identifier.hkuros246745-
dc.identifier.volume5-
dc.identifier.issue13-
dc.identifier.spage4732-
dc.identifier.epage4745-
dc.publisher.placeUnited States-

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