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Article: AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells

TitleAMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells
Authors
KeywordsMitogen activated protein kinase
Acetylation
Apoptosis
Cancer inhibition
Catalysis
Issue Date2012
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2012, v. 72 n. 17, p. 4394-4404 How to Cite?
AbstractAMP-activated protein kinase (AMPK), a biologic sensor for cellular energy status, has been shown to act upstream and downstream of known tumor suppressors. However, whether AMPK itself plays a tumor suppressor role in cancer remains unclear. Here, we found that the alpha2 catalytic subunit isoform of AMPK is significantly downregulated in hepatocellular carcinoma (HCC). Clinicopathologic analysis revealed that underexpression of AMPK-alpha2 was statistically associated with an undifferentiated cellular phenotype and poor patient prognosis. Loss of AMPK-alpha2 in HCC cells rendered them more tumorigenic than control cells both in vitro and in vivo. Mechanistically, ectopic expression of AMPK enhanced the acetylation and stability of p53 in HCC cells. The p53 deacetylase, SIRT1, was phosphorylated and inactivated by AMPK at Thr344, promoting p53 acetylation and apoptosis of HCC cells. Taken together, our findings suggest that underexpression of AMPK is frequently observed in HCC, and that inactivation of AMPK promotes hepatocarcinogenesis by destabilizing p53 in a SIRT1-dependent manner. Cancer Res; 72(17); 4394-404. (c)2012 AACR.
Persistent Identifierhttp://hdl.handle.net/10722/152619
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLee, CWen_US
dc.contributor.authorWong, LLYen_US
dc.contributor.authorTse, EYTen_US
dc.contributor.authorLiu, HFen_US
dc.contributor.authorLeong, VYLen_US
dc.contributor.authorLee, JMFen_US
dc.contributor.authorHardie, DGen_US
dc.contributor.authorNg, IOLen_US
dc.contributor.authorChing, YPen_US
dc.date.accessioned2012-07-16T09:44:12Z-
dc.date.available2012-07-16T09:44:12Z-
dc.date.issued2012en_US
dc.identifier.citationCancer Research, 2012, v. 72 n. 17, p. 4394-4404en_US
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/152619-
dc.description.abstractAMP-activated protein kinase (AMPK), a biologic sensor for cellular energy status, has been shown to act upstream and downstream of known tumor suppressors. However, whether AMPK itself plays a tumor suppressor role in cancer remains unclear. Here, we found that the alpha2 catalytic subunit isoform of AMPK is significantly downregulated in hepatocellular carcinoma (HCC). Clinicopathologic analysis revealed that underexpression of AMPK-alpha2 was statistically associated with an undifferentiated cellular phenotype and poor patient prognosis. Loss of AMPK-alpha2 in HCC cells rendered them more tumorigenic than control cells both in vitro and in vivo. Mechanistically, ectopic expression of AMPK enhanced the acetylation and stability of p53 in HCC cells. The p53 deacetylase, SIRT1, was phosphorylated and inactivated by AMPK at Thr344, promoting p53 acetylation and apoptosis of HCC cells. Taken together, our findings suggest that underexpression of AMPK is frequently observed in HCC, and that inactivation of AMPK promotes hepatocarcinogenesis by destabilizing p53 in a SIRT1-dependent manner. Cancer Res; 72(17); 4394-404. (c)2012 AACR.-
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Researchen_US
dc.subjectMitogen activated protein kinase-
dc.subjectAcetylation-
dc.subjectApoptosis-
dc.subjectCancer inhibition-
dc.subjectCatalysis-
dc.titleAMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cellsen_US
dc.typeArticleen_US
dc.identifier.emailWong, LLY: lapywong@hku.hken_US
dc.identifier.emailTse, EYT: edithtse@graduate.hku.hken_US
dc.identifier.emailLiu, HF: liumico@hku.hken_US
dc.identifier.emailLeong, VYL: vleong@hkucc.hku.hken_US
dc.identifier.emailLee, JMF: joyce@pathology.hku.hken_US
dc.identifier.emailNg, IOL: iolng@hku.hken_US
dc.identifier.emailChing, YP: ypching@hku.hken_US
dc.identifier.authorityChing, YP=rp00469en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-12-0429-
dc.identifier.pmid22728651-
dc.identifier.pmcidPMC3433393-
dc.identifier.scopuseid_2-s2.0-84865793242-
dc.identifier.hkuros200812en_US
dc.identifier.volume72-
dc.identifier.issue17-
dc.identifier.spage4394-
dc.identifier.epage4404-
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000308565600013-
dc.publisher.placeUnited States-

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