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

Kai Fu, Xin Sun, Xue Xia, Ryan P. Hobbs, Yajuan Guo, Pierre A. Coulombe, Fengyi Wan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalCancer medicine
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Skin Neoplasms
Mitosis
Keratinocytes
DNA Damage
Survival
Growth
DNA Repair
Transgenic Mice
NF-kappa B
Basal Cell Carcinoma
Neoplasms
Down-Regulation
Skin
DNA

Keywords

  • DNA damage responses
  • NF-κB
  • Sam68
  • skin cancer

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Fu, K., Sun, X., Xia, X., Hobbs, R. P., Guo, Y., Coulombe, P. A., & Wan, F. (Accepted/In press). Sam68 is required for the growth and survival of nonmelanoma skin cancer. Cancer medicine. https://doi.org/10.1002/cam4.2513

Sam68 is required for the growth and survival of nonmelanoma skin cancer. / Fu, Kai; Sun, Xin; Xia, Xue; Hobbs, Ryan P.; Guo, Yajuan; Coulombe, Pierre A.; Wan, Fengyi.

In: Cancer medicine, 01.01.2019.

Research output: Contribution to journalArticle

Fu, Kai ; Sun, Xin ; Xia, Xue ; Hobbs, Ryan P. ; Guo, Yajuan ; Coulombe, Pierre A. ; Wan, Fengyi. / Sam68 is required for the growth and survival of nonmelanoma skin cancer. In: Cancer medicine. 2019.
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