J Cancer 2018; 9(18):3373-3381. doi:10.7150/jca.25083
Short Research Communication
Is Ras a potential target in treatment against cutaneous squamous cell carcinoma?
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, 210042, China
# These authors contribute to this work equally.
Li L, Li M, Xu S, Bu W, Zhang M, Gu H, Chen X. Is Ras a potential target in treatment against cutaneous squamous cell carcinoma?. J Cancer 2018; 9(18):3373-3381. doi:10.7150/jca.25083. Available from http://www.jcancer.org/v09p3373.htm
Hyperactive retrovirus-associated DNA sequence (Ras) genes have been found in human cancers and are involved in cancer pathogenesis. Salirasib, one anti-Ras compound, was reported to exhibit antitumoral effects, but its role remains unclear in cutaneous squamous cell carcinoma (cSCC). In our study, salirasib treatment led to deregulation of c-Raf, ERK and Akt signaling, blockage of MTOR signaling, interruption on Beclin 1-related autophagy regulation, activation of apoptosis and down-regulation of some cell cycle regulatory proteins in primary human epidermal keratinocyte (HEK)s, but did not exhibit similar effects in the human cSCC cell line COLO-16. MEK inhibitor U0126 can lead to dephosphorylation of MTOR and Rictor in COLO-16 cells; however, c-Raf was not yet down-regulated after salirasib treatment in the presence of U0126. Furthermore, we verified that the Ras activity could be suppressed by salirasib, and there was no loss-of-function mutation in c-Raf in HEKs and COLO-16 cells. In summary, salirasib does not exhibit antitumoral effects in the cSCC cells in assays in vitro. We speculated that the disability of signaling transmission from Ras to c-Raf in COLO-16 cells might contribute to the ineffective performance of salirasib.
Keywords: cutaneous squamous cell carcinoma, keratinocyte, salirasib, Ras, p53