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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\u2010autocrine signaling in syngeneic wildtype and HGF transgenic mouse hosts. We also used small molecule drugs in preclinical mouse models to confirm that Ezrin is one of the downstream molecules mediating HGF\/Met signaling\u2010induced metastasis in melanoma. We conclude that Ezrin is a key downstream factor involved in the regulation of HGF\/Met signaling\u2010induced metastasis and demonstrate a link between Ezrin and HGF\/Met\/MAPK\/Sp1 activation in the metastatic process. Our data indicate that Ezrin represents a promising therapeutic target for patients bearing tumors with activated HGF\/Met signaling.<\/jats:p>","DOI":"10.1002\/ijc.31196","type":"journal-article","created":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T08:28:40Z","timestamp":1512548920000},"page":"1652-1663","source":"Crossref","is-referenced-by-count":24,"title":["Ezrin mediates both HGF\/Met autocrine and non\u2010autocrine signaling\u2010induced metastasis in melanoma"],"prefix":"10.1002","volume":"142","author":[{"given":"Liping","family":"Huang","sequence":"first","affiliation":[{"name":"Laboratory of Cancer Biology and Genetics Center for Cancer Research, National Cancer Institutes, National Institutes of Health Bethesda MD 20892\u20104264"},{"name":"Department of Obstetrics and Gynecology Nanfang Hospital, Southern Medical University Guangzhou 510515 People's Republic of 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