Objective: The SAM- and SH3-domain containing 1 gene (SASH1) has been considered as a tumor suppressor in some cancers. Nevertheless, the effect of SASH1 on the proliferation and invasion of human skin squamous cell carcinoma (cSCC) remains poorly understood. Therefore, the purpose of the present study was to observe the potential role of SASH1 in cSCC and investigate its underlying mechanisms.
Methods: The overexpression of SASH1 was constructed by transfecting the pcDNA3.1/SASH1 vector into SCL-1 and A431 cells, and SASH1 knockdown was generated by transfecting the SASH1 siRNA into cSCC cells. Then, cell proliferation, invasion, apoptosis, and Akt pathway were observed.
Results: The expression levels of SASH1 mRNA and protein were greatly reduced in cSCC cells. The overexpression of SASH1 inhibited the viability and invasion of cSCC cells, while its knockdown induced the viability and invasion of cSCC cells. The overexpression of SASH1 also suppressed the expression levels of p-Akt and its target genes, including cyclin D1, Bcl-2, and metal matrix proteinase 2(MMP-2). By contrast, SASH1 knockdown exerted the opposite role. Furthermore, inhibition of Akt obviously decreased the inducible effect of cSCC knockdown on the proliferation and invasion of cSCC cells.
Conclusion: Overall, these results found that SASH1 inhibits the proliferation and invasion of cSCC cells via suppressing Akt cascade, indicating a tumor inhibitory effect of SASH1 in cSCC cells.
Keywords: human skin squamous cell carcinoma, SASH1, Akt