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Mammalian SIRT 2 inhibits keratin 19 expression and is a tumor suppressor in skin
Author(s) -
Ming Mei,
Qiang Lei,
Zhao Baozhong,
He YuYing
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12323
Subject(s) - sirt2 , sirtuin , cancer research , biology , gene knockdown , keratinocyte , keratin , skin cancer , cancer , microbiology and biotechnology , gene , cell culture , genetics , acetylation
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.