title: Src42A modulates tumor invasion and cell death via Ben/dUev1a-mediated JNK activation in Drosophila.
abstract: Loss of the cell polarity gene could cooperate with oncogenic Ras to drive tumor growth and invasion, which critically depends on the c-Jun N-terminal Kinase (JNK) signaling pathway in Drosophila. By performing a genetic screen, we have identified Src42A, the ortholog of mammalian Src, as a key modulator of both Ras(V12)/lgl(-/-) triggered tumor invasion and loss of cell polarity gene-induced cell migration. Our genetic study further demonstrated that the Bendless (Ben)/dUev1a ubiquitin E2 complex is an essential regulator of Src42A-induced, JNK-mediated cell migration. Furthermore, we showed that ectopic Ben/dUev1a expression induced invasive cell migration along with increased MMP1 production in wing disc epithelia. Moreover, Ben/dUev1a could cooperate with Ras(V12) to promote tumor overgrowth and invasion. In addition, we found that the Ben/dUev1a complex is required for ectopic Src42A-triggered cell death and endogenous Src42A-dependent thorax closure. Our data not only provide a mechanistic insight into the role of Src in development and disease but also propose a potential oncogenic function for Ubc13 and Uev1a, the mammalian homologs of Ben and dUev1a.
authors.affiliation: Department of Interventional Radiology, Shanghai Key Laboratory of Signaling and Disease Research, Shanghai 10th People's Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.forename: Y
authors.initials: Y
authors.lastname: Shao
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Xue
mesh_terms: D000818:Animals; D016923:Cell Death; D002465:Cell Movement; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology*; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D014921:Wings, Animal / Q000201:enzymology / Q000254:growth & development / Q000473:pathology; D018631:ras Proteins / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; C583339:Uev1a protein, Drosophila; D016392:Proto-Oncogene Proteins pp60(c-src); C100382:Src42A protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D018631:ras Proteins