Lessons from border cell migration in the Drosophila ovary: A role for myosin VI in dissemination of human ovarian cancer

Proceedings of the National Academy of Sciences of the United States of America - Tập 101 Số 21 - Trang 8144-8149 - 2004
Hiroyuki Yoshida1, Wenjun Cheng1, Jamie Hung1, Denise J. Montell1, Erika R. Geisbrecht1, Daniel Rosen1, Jinsong Liu1, Honami Naora1
1Departments of Molecular Therapeutics, Pathology, and Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; and Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 101 Số 21

8144-8149

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