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SIRT6 Promotes COX-2 Expression and Acts as an Oncogene in Skin Cancer

Year: 2014
Type: article
Abstract: SIRT6 is a SIR2 family member that regulates multiple molecular pathways involved in metabolism, genomic stability, and aging. It has been proposed previously that SIRT6 is a tumor suppressor in cancer. Here, we challenge this concept by presenting evidence that skin-specific deletion of SIRT6 in the mouse inhibits skin tumorigenesis. SIRT6 promoted expression of COX-2 by repressing AMPK signaling, thereby increasing cell proliferation and survival in the skin epidermis. SIRT6 expression in skin keratinocytes was increased by exposure to UVB light through activation of the AKT pathway. Clinically, we found that SIRT6 was upregulated in human skin squamous cell carcinoma. Taken together, our results provide evidence that SIRT6 functions as an oncogene in the epidermis and suggest greater complexity to its role in epithelial carcinogenesis.
DOI: 10.1158/0008-5472.can-14-1308
Authors: Mei Ming, Weinong Han, Baozhong Zhao, Nagalingam R. Sundaresan, Chu-Xia Deng, Mahesh P. Gupta, Yu-Ying He
Language: English
Field: Medicine
Open Access status: green
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Environmental Health Sciences, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1156963993, Activation of sirtuins to prevent adverse cardiac remodeling after CABG, G2252753298, Re-Engineering Translational Research at the University of Chicago, G4650537345, Translational Research at The University of Chicago (UL1), Mechanisms of UVA-induced skin cancer, Blocking cardiac toxicity of anticancer drugs, Cancer Center Support Grant
OpenAlex ID: W2055831721
FWCI: 6.955
Cites: 61
Cited by: 113
Related to: 10