PT  - JOURNAL ARTICLE
AU  - Ming, Mei
AU  - Han, Weinong
AU  - Zhao, Baozhong
AU  - Sundaresan, Nagalingam R.
AU  - Deng, Chu-Xia
AU  - Gupta, Mahesh P.
AU  - He, Yu-Ying
TI  - SIRT6 Promotes COX-2 Expression and Acts as an Oncogene in Skin Cancer
AID  - 10.1158/0008-5472.CAN-14-1308
DP  - 2014 Oct 15
TA  - Cancer Research
PG  - 5925--5933
VI  - 74
IP  - 20
4099  - http://cancerres.aacrjournals.org/content/74/20/5925.short
4100  - http://cancerres.aacrjournals.org/content/74/20/5925.full
SO  - Cancer Res2014 Oct 15; 74
AB  - 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. Cancer Res; 74(20); 5925–33. ©2014 AACR.