title: 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.
authors.affiliation: Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois.
authors.forename: Mei
authors.initials: M
authors.lastname: Ming
authors.affiliation: Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois.
authors.forename: Weinong
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois.
authors.forename: Baozhong
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Surgery, Committee on Cellular and Molecular Physiology, University of Chicago, Chicago, Illinois. Division of Biological Sciences, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, India.
authors.forename: Nagalingam R
authors.initials: NR
authors.lastname: Sundaresan
authors.affiliation: National Institute of Diabetes, Digestive and Kidney Diseases, US NIH, Bethesda, Maryland.
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
authors.affiliation: Department of Surgery, Committee on Cellular and Molecular Physiology, University of Chicago, Chicago, Illinois.
authors.forename: Mahesh P
authors.initials: MP
authors.lastname: Gupta
authors.affiliation: Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois. yyhe@medicine.bsd.uchicago.edu.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: He
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004790:Enzyme Induction; D004817:Epidermis / Q000201:enzymology / Q000473:pathology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009857:Oncogenes; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020871:RNA Stability; D037761:Sirtuins / Q000502:physiology*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics; D014466:Ultraviolet Rays
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D000263:Adenylate Kinase; C516592:SIRT6 protein, human; D037761:Sirtuins