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In our study, we established an orthotopic ovarian cancer model, wherein FILIP1L expression can be regulated <jats:italic>in vivo<\/jats:italic>. Using this model, we observed that expression of FILIP1L in ovarian cancer cells inhibited spontaneous lung metastasis. Experimental lung metastases (established <jats:italic>via<\/jats:italic> tail vein injection of cancer cells) as well as the extravasation step of metastasis were not inhibited by FILIP1L, suggesting that FILIP1L inhibits the earlier steps of metastasis such as invasion and intravasation. FILIP1L inhibited matrix metalloproteinase (MMP)\u2010dependent invasion <jats:italic>in vivo. MMP3<\/jats:italic>, \u2010<jats:italic>7<\/jats:italic> and \u2010<jats:italic>9<\/jats:italic> were transcriptionally downregulated, and MMP9 protein expression and activity were inhibited in FILIP1L\u2010expressing tumors. Importantly, overexpression of MMP9 compensated for the anti\u2010invasive activity of FILIP1L. Furthermore, our studies suggest that FILIP1L regulates invasion and metastasis by inhibiting components of the WNT signaling pathway. FILIP1L expression reduced the induction of WNT target genes such as <jats:italic>MMP3<\/jats:italic>, \u2010<jats:italic>7<\/jats:italic> and \u2010<jats:italic>9<\/jats:italic>, and \u03b2\u2010catenin\u2010directed transcriptional activity, suggesting inhibition of the canonical WNT pathway. Nuclear \u03b2\u2010catenin, an indicator of an active canonical WNT pathway, was reduced in FILIP1L\u2010expressing tumors. Overall, these findings suggest that FILIP1L reduces \u03b2\u2010catenin levels, which may lead to the transcriptional downregulation of WNT target genes such as MMPs, resulting in inhibition of metastasis. Modulation of FILIP1L expression has the potential to be a target for cancer therapy.<\/jats:p>","DOI":"10.1002\/ijc.28662","type":"journal-article","created":{"date-parts":[[2013,12,11]],"date-time":"2013-12-11T04:38:40Z","timestamp":1386736720000},"page":"48-60","source":"Crossref","is-referenced-by-count":48,"title":["Filamin A interacting protein 1\u2010like inhibits WNT signaling and MMP expression to suppress cancer cell invasion and metastasis"],"prefix":"10.1002","volume":"135","author":[{"given":"Mijung","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Surgery Albert Einstein College of Medicine of Yeshiva University Bronx NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery Albert Einstein College of Medicine of Yeshiva University Bronx 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