Sam68 is required for the growth and survival of nonmelanoma skin cancer

Cancer Medicine

Ryan P. Hobbs¹  Pierre A. Coulombe¹  Fengyi Wan¹  Xin Sun¹  Xue Xia¹  Yajuan Guo¹  Kai Fu² 

[1] Department of Biochemistry and Molecular Biology Bloomberg School of Public Health Johns Hopkins University Baltimore MD USA;Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine Xiangya Hospital Central South University Changsha Hunan China;

关键词: DNA damage responses;    NF‐κB;    Sam68;    skin cancer;   

DOI  :  10.1002/cam4.2513

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown