1. Sam68 is required for the growth and survival of nonmelanoma skin cancer
- Author
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Fengyi Wan, Xue Xia, Ryan P. Hobbs, Yajuan Guo, Kai Fu, Xin Sun, and Pierre A. Coulombe
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Skin Neoplasms ,DNA Repair ,DNA repair ,DNA damage ,Mice, Transgenic ,Zinc Finger Protein Gli2 ,lcsh:RC254-282 ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Mitosis ,Original Research ,Cancer Biology ,Adaptor Proteins, Signal Transducing ,integumentary system ,skin cancer ,business.industry ,NF‐κB ,NF-kappa B ,RNA-Binding Proteins ,NF-κB ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Sam68 ,Cancer research ,Female ,Skin cancer ,Signal transduction ,DNA damage responses ,business ,Keratinocyte ,DNA Damage ,Signal Transduction - 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., Here, we report that 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.
- Published
- 2019