Journal
ONCOTARGET
Volume 7, Issue 19, Pages 27552-27566Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8487
Keywords
epithelial ovarian cancer; biomarker; prognosis; Migration-Inducting Gene 7; angiogenesis
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Funding
- Major National Science and Technology Project of China [2012ZX09102201-015]
- National Natural Science Foundation of China [81274131]
- Project Program of the State Key Laboratory of Natural Medicines of China Pharmaceutical University [JKGZ201107]
- US National Institutes of Health [U01AI95776, P30CA22453]
- Burroughs Wellcome Fund
- American Congress of Obstetricians and Gynecologists
- Wayne State University Maternal
- Perinatal and Child Health Initiative
- Wayne State University Office of the Vice President for Research
- Jiangsu Province Plan for Collaborative Innovation
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Epithelial ovarian carcinomas (EOC) cause more mortality than any other cancer of the female reproductive system. New therapeutic approaches to reduce EOC mortality have been largely unsuccessful due to the poor understanding of the mechanisms underlying EOC proliferation and metastasis. Progress in EOC treatment is further hampered by a lack of reliable prognostic biomarkers for early risk assessment. In this study, we identify that Migration-Inducting Gene 7 (MIG-7) is specifically induced in human EOC tissues but not normal ovaries or ovarian cyst. Ovarian MIG-7 expression strongly correlated with EOC progression. Elevated MIG-7 level at the time of primary cytoreductive surgery was a strong and independent predictor of poor survival of EOC patients. Cell and murine xenograft models showed that MIG-7 was required for EOC proliferation and invasion, and MIG-7 enhanced EOC-associated angiogenesis by promoting the expression of vascular endothelial growth factor. Inhibiting MIG-7 by RNA interference in grafted EOC cells retarded tumor growth, angiogenesis and improved host survival, and suppressing MIG-7 expression with a small molecule inhibitor D-39 identified from the medicinal plant Liriope muscari mitigated EOC growth and invasion and specifically abrogated the expression of vascular endothelial growth factor. Our data not only reveal a critical function of MIG-7 in EOC growth and metastasis and support MIG-7 as an independent prognostic biomarker for EOC, but also demonstrate that therapeutic targeting of MIG-7 is likely beneficial in the treatment of EOC.
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