Wnt/Snail Signaling Regulates Cytochrome c Oxidase and Glucose Metabolism
| العنوان: | Wnt/Snail Signaling Regulates Cytochrome c Oxidase and Glucose Metabolism |
|---|---|
| المؤلفون: | Hyun Min Jeon, Song Iy Han, Min Kyung Ju, Hye Gyeong Park, Gyesoon Yoon, Cho Hee Kim, Su Yeon Lee, Ho Sung Kang |
| المصدر: | Cancer Research. 72:3607-3617 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cancer Research, Epithelial-Mesenchymal Transition, Breast Neoplasms, Snail, Carbohydrate metabolism, Transfection, Electron Transport Complex IV, Cell Line, Tumor, biology.animal, Humans, Cytochrome c oxidase, Glycolysis, RNA, Small Interfering, beta Catenin, biology, Chemistry, Wnt signaling pathway, LRP6, LRP5, Cell biology, Wnt Proteins, Glucose, Oncology, biology.protein, Female, Snail Family Transcription Factors, Signal transduction, Transcription Factor 7-Like 2 Protein, Signal Transduction, Transcription Factors |
| الوصف: | 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. Cancer Res; 72(14); 3607–17. ©2012 AACR. |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b64de85ee993644bb3c4b7f91f2ffc4Test https://doi.org/10.1158/0008-5472.can-12-0006Test |
| رقم الانضمام: | edsair.doi.dedup.....8b64de85ee993644bb3c4b7f91f2ffc4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
|---|