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We previously identified Sohlh2 as an important inhibitor of ovarian cancer cell proliferation. However, the function of Sohlh2 in cell migration and invasion remains unknown. In this paper, we report a novel Sohlh2 to MMP9 signaling pathway in the invasive ovarian cancer. Using immunohistochemistry staining, we revealed Sohlh2 expression was inversely correlated with the invasive human ovarian cancers. In vitro experiments, forced expression of Sohlh2 led to a significant reduction in cancer cell migration and invasion. Conversely, silencing of Sohlh2 enhanced ovarian cancer cell migration and invasion. Experiments using nude mice demonstrated that the ectopic Sohlh2 expression inhibited the HO8910 cell capability of the metastasis to the lungs and livers. Ectopic overexpression of Sohlh2 in the invasive HO8910 cells reduced the MMP9 expression, whereas Sohlh2 knockdown from the non\u2010invasive, SKOV3 cells increased the MMP9 expression. Promoter activation and binding analyses indicated that Sohlh2 repressed the MMP9 expression by directly acting on the MMP9 gene promoter. Inhibition of MMP9 dramatically blocked the Sohlh2 knockdown\u2010enhanced SKOV3 cell invasion, and ectopic expression of MMP9 compensated for the anti\u2010invasive activity of Sohlh2 in HO8910 cells. Overall, these results demonstrate for the first time that Sohlh2 functions as a tumor metastasis suppressor. Modulation of Sohlh2 expression has the potential to be a target for cancer therapy. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22355","type":"journal-article","created":{"date-parts":[[2015,7,8]],"date-time":"2015-07-08T07:05:11Z","timestamp":1436339111000},"page":"1127-1137","source":"Crossref","is-referenced-by-count":20,"title":["Sohlh2 inhibits human ovarian cancer cell invasion and metastasis by transcriptional inactivation of MMP9"],"prefix":"10.1002","volume":"55","author":[{"given":"Haiyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, School of Medicine Key Laboratory of the Ministry of Education for Experimental Teratology Shandong University  Jinan PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Medicine Shandong University Jinan PR 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