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Published Online October 9, 2003
Science DOI: 10.1126/science.1088474

Reports

Submitted on June 26, 2003
Accepted on September 29, 2003

A Genetic Screen in Drosophila for Metastatic Behavior

Raymond A. Pagliarini 1 Tian Xu 1*

1 Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.

* To whom correspondence should be addressed. E-mail: tian.xu{at}yale.edu.

A genetic screen has been designed in Drosophila to interrogate the genome for mutations sufficient to cause noninvasive tumors of the eye disc to invade neighboring or distant tissues. From this screen, we observe that cooperation between oncogenic RasV12 expression and inactivation of any one of a number of genes affecting cell polarity leads to metastatic behavior, including basement membrane degradation, loss of E-cadherin expression, migration, invasion, and secondary tumor formation. Inactivation of these cell polarity genes cannot drive metastatic behavior alone or in combination with other tumor-initiating alterations, suggesting the oncogenic background makes a distinct contribution toward metastatic development.


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