Open AccessSam68 is required for the growth and survival of nonmelanoma skin cancer
Author(s) -
Fu Kai,
Sun Xin,
Xia Xue,
Hobbs Ryan P.,
Guo Yajuan,
Coulombe Pierre A.,
Wan Fengyi
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2513
Subject(s) - skin cancer , keratinocyte , cancer research , biology , dna damage , dna repair , tumor initiation , cancer , basal cell carcinoma , microbiology and biotechnology , pathology , carcinogenesis , medicine , dna , cell culture , genetics , basal cell
Although targeting DNA repair signaling pathways has emerged as a promising therapeutic for skin cancer, the relevance of DNA damage responses (DDR) in the development and survival of nonmelanoma skin cancer (NMSC), the most common type of skin cancer, remains obscure. Here, we report that Src‐associated substrate during mitosis of 68 kDa (Sam68), an early signaling molecule in DDR, is elevated in skin tumor tissues derived from NMSC patients and skin lesions from Gli2 ‐transgenic mice. Downregulation of Sam68 impacts the growth and survival of human tumor keratinocytes and genetic ablation of Sam68 delays the onset of basal cell carcinomas (BCC) in Gli2 ‐transgenic mice. Moreover, Sam68 plays a critical role in DNA damage‐induced DNA repair and nuclear factor kappa B (NF‐κB) signaling pathways in keratinocytes, hence conferring keratinocyte sensitivity to DNA damaging agents. Together, our data reveal a novel function of Sam68 in regulating DDR in keratinocytes that is crucial for the growth and survival of NMSC.