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Molecular and Cellular Biology, March 2008, p. 1964-1973, Vol. 28, No. 6
0270-7306/08/$08.00+0     doi:10.1128/MCB.01743-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

awd, the Homolog of Metastasis Suppressor Gene Nm23, Regulates Drosophila Epithelial Cell Invasion{triangledown} ,{dagger}

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

Received 22 September 2007/ Returned for modification 23 October 2007/ Accepted 7 January 2008

Border cell migration during Drosophila melanogaster oogenesis is a highly pliable model for studying epithelial to mesenchymal transition and directional cell migration. The process involves delamination of a group of 6 to 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 platelet-derived growth factor/vascular endothelial growth factor family of growth factor, or Pvf, emanating from the oocyte, although Drosophila epidermal growth factor 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 overexpression 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 overexpression in the border cells results in stalled migration and can revert the phenotype of overexpressing 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.

* Corresponding author. Mailing address for Tien Hsu: Medical University of South Carolina, Hollings Cancer Center, 86 Jonathan Lucas St., Room 330, Charleston, SC 29425. Phone: (843) 792-0638. Fax: (843) 792-5002. E-mail: hsut{at}musc.edu. Mailing address for Vincent Dammai: Medical University of South Carolina, Hollings Cancer Center, 86 Jonathan Lucas St., Room 316, Charleston, SC 29425. Phone: (843) 792-7568. Fax: (843) 792-5002. E-mail: dammaiv{at}musc.edu

{triangledown} Published ahead of print on 22 January 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, March 2008, p. 1964-1973, Vol. 28, No. 6
0270-7306/08/$08.00+0     doi:10.1128/MCB.01743-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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