Regulation of SIRT2 by Wnt/β-catenin signaling pathway in colorectal cancer cells
| Autor: | Heidi L. Weiss, B. Mark Evers, Tomoko Sengoku, Michael C. Alstott, Yuning Zhou, Chang Li, Ji Tae Kim, Qingding Wang |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell signaling Colorectal cancer Cellular differentiation SIRT2 Article Oxidative Phosphorylation 03 medical and health sciences Sirtuin 2 0302 clinical medicine medicine Humans Promoter Regions Genetic Molecular Biology beta Catenin Cell Proliferation Messenger RNA Gene knockdown biology Chemistry Wnt signaling pathway Cell Differentiation Cell Biology HCT116 Cells medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology Gene Knockdown Techniques 030220 oncology & carcinogenesis Sirtuin Cancer research biology.protein Caco-2 Cells Colorectal Neoplasms HT29 Cells |
| Zdroj: | Biochim Biophys Acta Mol Cell Res |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2021.118966 |
| Popis: | Activation of the Wnt/β-catenin pathway is one of the hallmarks of colorectal cancer (CRC). Sirtuin 2 (SIRT2) protein has been shown to inhibit CRC proliferation. Previously, we reported that SIRT2 plays an important role in the maintenance of normal intestinal cell homeostasis. Here, we show that SIRT2 is a direct target gene of Wnt/β-catenin signaling in CRC cells. Inhibition or knockdown of Wnt/β-catenin increased SIRT2 promoter activity and mRNA and protein expression, whereas activation of Wnt/β-catenin decreased SIRT2 promoter activity and expression. β-Catenin was recruited to the promoter of SIRT2 and transcriptionally regulated SIRT2 expression. Wnt/β-catenin inhibition increased mitochondrial oxidative phosphorylation (OXPHOS) and CRC cell differentiation. Moreover, inhibition of OXPHOS attenuated the differentiation of CRC cells induced by Wnt/β-catenin inhibition. In contrast, inhibition or knockdown of SIRT2 decreased, while overexpression of SIRT2 increased, OXPHOS activity and differentiation in CRC cells. Consistently, inhibition or knockdown or SIRT2 attenuated the differentiation induced by Wnt/β-catenin inhibition. These results demonstrate that SIRT2 is a novel target gene of the Wnt/β-catenin signaling and contributes to the differentiation of CRC cells. |
| Databáze: | OpenAIRE |
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