MCB Accepts, published online ahead of print on 22 January 2008

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Mol. Cell. Biol. doi:10.1128/MCB.01743-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

awd, the homolog of metastasis suppressor gene Nm23, regulates Drosophila epithelial cell invasion

Gouthami Nallamothu, Julie A. Woolworth, Vincent Dammai^*, and Tien Hsu^*

Department of Pathology and Laboratory Medicine, and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA

^* To whom correspondence should be addressed. Email: dammaiv{at}musc.edu. hsut{at}musc.edu.

Border cell migration during Drosophila oogenesis is a highly pliable model for studying epithelial to mesenchymal transition (EMT) and directional cell migration. The process involves delamination of a group of 6-10 follicle cells from the epithelium followed by guided migration and invasion through the nurse cell complex toward the oocyte. The guidance cue is mainly provided by the homolog of PDGF/VEGF family of growth factor, or Pvf, emanating from the oocyte, although the Drosophila EGF receptor signaling also plays an auxiliary role. Earlier studies implicated a stringent control of the strength of Pvf-mediated signaling since both down-regulation of Pvf and over-expression of active Pvf receptor (Pvr) resulted in stalled border cell migration. Here we show that the metastasis suppressor gene homolog Nm23/awd is a negative regulator of border cell migration. Its down-regulation allows for optimal spatial signaling from two crucial pathways, Pvr and JAK/STAT. Its over-expression in the border cells results in stalled migration, and can revert the phenotype of over-expressing constitutive Pvr or dominant-negative dynamin. This is a rare example demonstrating the relevance of a metastasis suppressor gene function utilized in a developmental process involving cell invasion.

This article has been cited by other articles:

• Woolworth, J. A., Nallamothu, G., Hsu, T. (2009). The Drosophila Metastasis Suppressor Gene Nm23 Homolog, awd, Regulates Epithelial Integrity during Oogenesis. Mol. Cell. Biol. 29: 4679-4690 [Abstract] [Full Text]