Netrin-1 promoted pancreatic cancer cell proliferation by upregulation of Mdm2

Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to result from the ability of netrin-1 secretions to stimulate survival when bound to associated receptors. The objective of this study was to determine the role of netrin-1 in pancreatic cancer cell proliferation in vitro. Our results revealed that netrin-1 overexpression promoted while its silence inhibited two pancreatic cancer cell lines. At the molecular level, we found that netrin-1 promoted cell proliferation by upregulation of murine double minute 2 (Mdm2). As a result, p53 protein contents were reduced in cells overexpressing netrin-1. Therefore, our data suggests the presence of a previously unknown network in the proliferation and progression of pancreatic cancer cells.