title: Migration-inducing gene 7 promotes tumorigenesis and angiogenesis and independently predicts poor prognosis of epithelial ovarian cancer.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA.|Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.|Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Detroit, Michigan, USA.
authors.forename: Bihui
authors.initials: B
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural Products and Jiangsu Key Laboratory of Traditional Chinese Medicine (TCM) Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.|Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Yin
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.|Yale Stem Cell Center, Yale University, New Haven, Connecticut, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Products and Jiangsu Key Laboratory of Traditional Chinese Medicine (TCM) Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Natural Products and Jiangsu Key Laboratory of Traditional Chinese Medicine (TCM) Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Lou
authors.affiliation: Department of Pathology, Wayne State University, Detroit, Michigan, USA.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Center and Department of Oncology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Shijie
authors.initials: S
authors.lastname: Sheng
authors.affiliation: State Key Laboratory of Natural Products and Jiangsu Key Laboratory of Traditional Chinese Medicine (TCM) Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Kou
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.|Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Detroit, Michigan, USA.|Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Center and Department of Oncology, Wayne State University, Detroit, Michigan, USA.|Department of Immunology and Microbiology, Wayne State University, Detroit, Michigan, USA.|Mucosal Immunology Studies Team, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Products and Jiangsu Key Laboratory of Traditional Chinese Medicine (TCM) Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
authors.forename: Boyang
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D014162:Transfection
chemical_list: D009363:Neoplasm Proteins; C482285:TOX4 protein, human
keywords: Migration-Inducting Gene 7; angiogenesis; biomarker; epithelial ovarian cancer; prognosis