Ezrin mediates both HGF/Met autocrine and non-autocrine signaling-induced metastasis in melanoma.

ABSTRACT: Aberrant HGF/Met signaling promotes tumor migration, invasion, and metastasis through both autocrine and non-autocrine mechanisms; however, the molecular downstream signaling mechanisms by which HGF/Met induces metastasis are incompletely understood. We here report that Ezrin expression is stimulated by HGF and correlates with activated HGF/Met, indicating that HGF/Met signaling regulates the expression of Ezrin. We show that HGF/Met signaling activates the transcription factor Sp1 through the MAPK pathway, and activated Sp1 can in turn directly bind to the promoter of Ezrin gene and regulate its transcription. Notably, knockdown of Ezrin expression by shRNAs inhibits the metastasis induced by either HGF/Met autocrine or non-autocrine signaling in syngeneic wildtype and HGF transgenic mous

SUBMITTER: Huang L 

PROVIDER: S-EPMC5814345 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature