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Metadherin (MTDH) is expressed in human ovarian cancer tissue and its expression inversely correlates with patients overall survival. Consistent with these studies, we observed MTDH expression in tissue specimens of FIGO Stage III ovarian carcinomas (72\/83 cases). However, we also observed this in normal human ovarian epithelial (OE) cells, which raised the question of whether MTDH\u2010variants with functional differences exist. We identified a novel MTDH exon 11 skipping variant (MTDHdel) which was seen at higher levels in ovarian cancer compared to benign OE cells. We analyzed MTDH\u2010binding partner interactions and found that 12 members of the small ribosomal subunit and several mRNA binding proteins bound stronger to MTDHdel than to wildtype MTDH which indicates differential effects on gene translation. Knockdown of MTDH in ovarian cancer cells reduced the amount of distant metastases and improved the survival of ovarian cancer\u2010bearing mice. Selective overexpression of the MTDHdel enhanced murine and human ovarian cancer progression and caused a malignant phenotype in originally benign human OE cells. MTDHdel was detectable in microdissected ovarian cancer cells of some human tissue specimens of ovarian carcinomas. In summary, we have identified a novel MTDH exon 11 skipping variant that shows enhanced binding to small ribosomal subunit members and that caused reduced overall survival of ovarian cancer bearing mice. Based on the findings in the murine system and in human tissues, MTDHdel must be considered a major promalignant factor for ovarian cancer.<\/jats:p>","DOI":"10.1002\/ijc.29289","type":"journal-article","created":{"date-parts":[[2014,10,25]],"date-time":"2014-10-25T09:11:12Z","timestamp":1414228272000},"page":"2328-2340","source":"Crossref","is-referenced-by-count":11,"title":["Metadherin exon 11 skipping variant enhances metastatic spread of ovarian cancer"],"prefix":"10.1002","volume":"136","author":[{"given":"Stefan","family":"Haug","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Freiburg University Medical Center University of Freiburg  Germany"},{"name":"Department of Psychiatry and Psychotherapy Freiburg University Medical Center University of Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Schnerch","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Freiburg 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