Mammalian SIRT 2 inhibits keratin 19 expression and is a tumor suppressor in skin

SIRT 2 is a member of the mammalian sirtuin family ( SIRT 1‐7). As compared with other sirtuins, SIRT 2 is found primarily in the cytoplasm. It regulates multiple physiological processes. However, the precise role of SIRT 2 in skin cancer remains unclear. Here, we show that SIRT 2 is downregulated in human skin cancer as compared with normal skin. SIRT 2 deletion increases tumor growth in mice. SIRT 2 knockdown upregulates the stem cell marker Keratin 19 (K19) in keratinocytes. In mice, SIRT 2 deletion up‐regulates K19 and K15 while it down‐regulates the differentiation marker Loricrin in both normal skin and tumors. In skin tumors but not normal skin, SIRT 2 deletion up‐regulates the stem cell marker CD 34 and increases the number of Ki67‐positive cells. These findings indicate that SIRT 2 is a tumor suppressor in the skin. Our findings add new insights into the role of SIRT 2 in the molecular pathogenesis of skin cancer.