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Wnt/Snail signaling regulates cytochrome C oxidase and glucose metabolism

DC Field Value Language
dc.contributor.authorLee, SY-
dc.contributor.authorJeon, HM-
dc.contributor.authorJu, MK-
dc.contributor.authorKim, CH-
dc.contributor.authorYoon, G-
dc.contributor.authorHan, SI-
dc.contributor.authorPark, HG-
dc.contributor.authorKang, HS-
dc.date.accessioned2013-04-22T06:39:45Z-
dc.date.available2013-04-22T06:39:45Z-
dc.date.issued2012-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/7800-
dc.description.abstractWnt signaling plays a critical role in embryonic development, and its deregulation is closely linked to the occurrence of a number of malignant tumors, including breast and colon cancer. The pathway also induces Snail-dependent epithelial-to-mesenchymal transition (EMT), which is responsible for tumor invasion and metastasis. In this study, we show that Wnt suppresses mitochondrial respiration and cytochrome C oxidase (COX) activity by inhibiting the expression of 3 COX subunits, namely, COXVIc, COXVIIa, and COXVIIc. We found that Wnt induced a glycolytic switch via increased glucose consumption and lactate production, with induction of pyruvate carboxylase (PC), a key enzyme of anaplerosis. In addition, Wnt-induced mitochondrial repression and glycolytic switching occurred through the canonical β-catenin/T-cell factor 4/Snail pathway. Short hairpin RNA-mediated knockdown of E-cadherin, a regulator of EMT, repressed mitochondrial respiration and induced a glycolytic switch via Snail activation, indicating that EMT may contribute to Wnt/Snail regulation of mitochondrial respiration and glucose metabolism. Together, our findings provide a new function for Wnt/Snail signaling in the regulation of mitochondrial respiration (via COX gene expression) and glucose metabolism (via PC gene expression) in tumor growth and progression.-
dc.language.isoen-
dc.subject.MESHBreast Neoplasms/*metabolism-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHElectron Transport Complex IV/*metabolism-
dc.subject.MESHEpithelial-Mesenchymal Transition-
dc.subject.MESHFemale-
dc.subject.MESHGlucose/*metabolism-
dc.subject.MESHHumans-
dc.subject.MESHRNA, Small Interfering/pharmacology-
dc.subject.MESHSignal Transduction-
dc.subject.MESHTranscription Factor 7-Like 2 Protein-
dc.subject.MESHTranscription Factors/*metabolism-
dc.subject.MESHTransfection-
dc.subject.MESHWnt Proteins/*metabolism-
dc.subject.MESHbeta Catenin/metabolism-
dc.titleWnt/Snail signaling regulates cytochrome C oxidase and glucose metabolism-
dc.typeArticle-
dc.identifier.pmid22637725-
dc.identifier.urlhttp://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=22637725-
dc.contributor.affiliatedAuthor윤, 계순-
dc.type.localJournal Papers-
dc.identifier.doi10.1158/0008-5472.CAN-12-0006-
dc.citation.titleCancer research-
dc.citation.volume72-
dc.citation.number14-
dc.citation.date2012-
dc.citation.startPage3607-
dc.citation.endPage3617-
dc.identifier.bibliographicCitationCancer research, 72(14):3607-3617, 2012-
dc.identifier.eissn1538-7445-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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