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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Ming M,Han W,Zhao B,Sundaresan NR,Deng CX,Gupta MP,He YYdoi
10.1158/0008-5472.CAN-14-1308subject
Has Abstractpub_date
2014-10-15 00:00:00pages
5925-33issue
20eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-14-1308journal_volume
74pub_type
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