Original ArticleIncreased semaphorin 3c expression promotes tumor growth and metastasis in pancreatic ductal adenocarcinoma by activating the ERK1/2 signaling pathway

- Sema3c is overexpressed and positively associated with tumor stage in pancreatic cancer.
- Overexpression of sema3c promotes pancreatic cancer proliferation and inhibited cell apoptosis.
- Sema3c promotes pancreatic cancer cell migration and invasion via the induction of EMT.
- Sema3c regulates pancreatic cancer cell EMT by activating the ERK1/2 signaling pathway.

Pancreatic cancer is characterized by neural alterations and aberrant expression of neural-specific factors. Semaphorins have been recognized as key contributors in axon guidance, the immune response and tumor progression. Recent studies have suggested the involvement of Semaphorin 3c (sema3c) in tumorigenesis and metastasis in numerous types of cancer, however, the clinical significance of sema3c and its role in the growth and metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we found that aberrant sema3c expression was positively associated with a particular tumor stage and correlated with poor survival of PDAC patients. Knockdown of sema3c attenuated proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a pancreatic cancer cell line and reduced PDAC cell tumorigenesis upon xenotransplantation into NOD/SCID mice. Overexpression of sema3c produced the opposite effects and promoted the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Overall, our findings demonstrate that aberrant expression of sema3c is correlated with poor prognosis of PDAC patients and promotes tumor growth and metastasis by activating ERK1/2 signaling pathway.