Awd, the homolog of metastasis suppressor gene Nm23, regulates Drosophila epithelial cell invasion.
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.
Nallamothu
Gouthami
G
Medical University of South Carolina, Hollings Cancer Center, 86 Jonathan Lucas St., Room 330, Charleston, SC 29425, USA.
Woolworth
Julie A
JA
Dammai
Vincent
V
Hsu
Tien
T
D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D034281:Dynamins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004705:Endocytosis; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System / Q000502:physiology; D009701:Nucleoside-Diphosphate Kinase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010053:Ovary / Q000166:cytology*; D011401:Promoter Regions, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D018123:Receptors, Interleukin / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D029721:Drosophila Proteins; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; C444499:dome protein, Drosophila; C438368:Pvr protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; D009701:Nucleoside-Diphosphate Kinase; C061642:awd protein, Drosophila; D034281:Dynamins; C439628:shi protein, Drosophila