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

Overview

Journal Cancer Res

Specialty Oncology

Date 2014 Oct 17

PMID 25320180

Citations 61

Authors

Mei Ming

Weinong Han

Baozhong Zhao

Nagalingam R Sundaresan

Chu-Xia Deng

Mahesh P Gupta

Yu-Ying He

Affiliations

Soon will be listed here.

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.

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