SIRT6 Promotes COX-2 Expression and Acts as an Oncogene in Skin Cancer
Copyright policy )SIRT6 Promotes COX-2 Expression and Acts as an Oncogene in Skin Cancer
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. Cancer Res; 74(20); 5925–33. ©2014 AACR.
- University of Chicago United States
- Indian Institute of Science Bangalore India
Skin Neoplasms, Carcinogenesis, Cell Survival, RNA Stability, Gene Expression, Animals, Humans, Sirtuins, Cells, Cultured, Cell Proliferation, Microbiology & Cell Biology, Mice, Knockout, Adenylate Kinase, Oncogenes, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Cyclooxygenase 2, Enzyme Induction, Carcinoma, Squamous Cell, Epidermis, Proto-Oncogene Proteins c-akt
Skin Neoplasms, Carcinogenesis, Cell Survival, RNA Stability, Gene Expression, Animals, Humans, Sirtuins, Cells, Cultured, Cell Proliferation, Microbiology & Cell Biology, Mice, Knockout, Adenylate Kinase, Oncogenes, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Cyclooxygenase 2, Enzyme Induction, Carcinoma, Squamous Cell, Epidermis, Proto-Oncogene Proteins c-akt
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).96 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!