SEMA6A overexpression inhibited tumor growth and metastasis in colorectal cancer

Colorectal cancer (CRC) is the fourth-leading cause of cancer-related mortality worldwide. Semaphorin 6A (SEMA6A) is a member of the semaphorin family, and its specific biological function in CRC progression remains unclear. Bioinformatics analysis revealed that SEMA6A expression was downregulated in CRC tissues and that low expression of SEMA6A was associated with a poor prognosis. Compared with those in normal colorectal epithelial cells, SEMA6A expression levels were lower in CRC cell lines. CACO2 and SW48 cells were chosen to construct stable SEMA6A-knockdown and SEMA6A-overexpressing cell lines. SEMA6A knockdown promoted CACO2 proliferation. Conversely, SEMA6A overexpression inhibited the proliferation and promoted the apoptosis of SW48 cells. Transwell and wound healing assays demonstrated that SEMA6A overexpression inhibited the invasion and migration ability of SW48 cells. SEMA6A overexpression might impede CRC cell migration and invasion by inhibiting the epithelial-to-mesenchymal transition, as evidenced by the downregulation of N-cadherin expression and the upregulation of E-cadherin expression in SW48 cells. To further validate the role of SEMA6A in CRC progression in vivo, transplanted tumor and liver metastasis mouse models were constructed in nude mice by injecting stable SEMA6A-overexpressing SW48 cell lines. SEMA6A overexpression inhibited tumor growth in SW48 tumor-bearing mice and the expression of Ki-67 in tumor tissues. In addition, SEMA6A overexpression resulted in a marked decrease in liver metastasis of CRC cells, with decreased numbers of hepatic metastatic nodules and infiltration of cancer cells. In summary, SEMA6A overexpression alleviated CRC progression by inhibiting tumor growth and metastasis both in vivo and in vitro.