Netrin-1 promotes gastric cancer cell proliferation and invasion via the receptor neogenin through PI3K/AKT signaling pathway.
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ABSTRACT: Netrin-1 is a laminin-related protein found to promote proliferation and invasion in multiple types of cancers. Recent studies have identified the function role of netrin-1 in several cancers; however, the influence of netrin-1 in human gastric cancer(GC) remains largely unknown. In this study, we found netrin-1 was upregulated in human GC tissues, where its expression correlated inversely with cancer stage and lymph node metastasis. We detected netrin-1 and its receptor knockdown significantly suppressed GC cells proliferation and invasion, while overexpression netrin-1 reversed these effects. Xenografted analyses using GC cells displayed significantly inhibition of tumor growth and metastasis by netrin-1 depletion. Furthermore, we identified that netrin-1 as a regulator of PI3K/AKT pathway to modulate GC cells proliferation and invasion abilities via its receptor neogenin. Taken together, our findings argued that netrin-1 and its receptor neogenin might act synergistically in promoting GC cells proliferation and invasion through the PI3K/AKT signaling pathway. It is conceivable that netrin-1 could be new therapeutic target to GC therapy.
SUBMITTER: Yin K
PROVIDER: S-EPMC5584240 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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