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Wnt/Snail signaling regulates cytochrome C oxidase and glucose metabolism

Authors
Lee, SY; Jeon, HM; Ju, MK; Kim, CH; Yoon, G; Han, SI; Park, HG; Kang, HS
Citation
Cancer research, 72(14):3607-3617, 2012
Journal Title
Cancer research
ISSN
0008-54721538-7445
Abstract
Wnt 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.
MeSH terms
Breast Neoplasms/*metabolismCell Line, TumorElectron Transport Complex IV/*metabolismEpithelial-Mesenchymal TransitionFemaleGlucose/*metabolismHumansRNA, Small Interfering/pharmacologySignal TransductionTranscription Factor 7-Like 2 ProteinTranscription Factors/*metabolismTransfectionWnt Proteins/*metabolismbeta Catenin/metabolism
DOI
10.1158/0008-5472.CAN-12-0006
PMID
22637725
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
윤, 계순
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