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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-05, Vol.101 (21), p.8144-8149
Main Authors: Yoshida, H, Cheng, W, Hung, J, Montell, D, Geisbrecht, E, Rosen, D, Liu, J, Naora, H
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Carcinoma
Cell Division
Cell Line, Tumor
Cell lines
Cell Movement
Cell Size
Drosophila
Drosophila - cytology
Epithelial cells
Female
Insects
Mice
Mice, Nude
Molecular biology
Myosin Type IV - biosynthesis
Myosin Type IV - deficiency
Myosin Type IV - genetics
Myosin Type IV - metabolism
Neoplasm Metastasis
Neoplasm Transplantation
Oligomers
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Ovaries
Ovary - cytology
Ovary - metabolism
Ovary - pathology
Physical Sciences
RNA, Antisense - genetics
RNA, Antisense - metabolism
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Small interfering RNA
Transfection
Tumors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0400400101