Lessons from border cell migration in the Drosophila ovary: A role for myosin VI in dissemination of human ovarian cancer.
Dissemination of ovarian cancer is a major clinical challenge and is poorly understood at the molecular level due to a lack of suitable experimental models. During normal development of the Drosophila ovary, a dynamic process called border cell migration occurs that resembles the migratory behavior of human ovarian cancer cells. In this study, we found that myosin VI, a motor protein that regulates border cell migration, is abundantly expressed in high-grade ovarian carcinomas but not in normal ovary and ovarian cancers that behave indolently. Inhibiting myosin VI expression in high-grade ovarian carcinoma cells impeded cell spreading and migration in vitro. Optical imaging and histopathologic studies revealed that inhibiting myosin VI expression reduces tumor dissemination in nude mice. Therefore, using genetic analysis of border cell migration in Drosophila is a powerful approach to identify novel molecules that promote ovarian cancer dissemination and represent potential therapeutic targets.
Yoshida
Hiroyuki
H
Department of Molecular Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Cheng
Wenjun
W
Hung
Jamie
J
Montell
Denise
D
Geisbrecht
Erika
E
Rosen
Daniel
D
Liu
Jinsong
J
Naora
Honami
H
D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D048429:Cell Size; D004330:Drosophila / Q000166:cytology*; D005260:Female; D051379:Mice; D008819:Mice, Nude; D025121:Myosin Type IV / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010053:Ovary / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
D016372:RNA, Antisense; D034741:RNA, Small Interfering; D025121:Myosin Type IV