Src42A modulates tumor invasion and cell death via Ben/dUev1a-mediated JNK activation in Drosophila
Src42A modulates tumor invasion and cell death via Ben/dUev1a-mediated JNK activation in Drosophila
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.
- Tongji University China (People's Republic of)
Cell Death, MAP Kinase Signaling System, Proto-Oncogene Proteins pp60(c-src), JNK Mitogen-Activated Protein Kinases, Enzyme Activation, Drosophila melanogaster, Cell Movement, Neoplasms, Ubiquitin-Conjugating Enzymes, ras Proteins, Animals, Drosophila Proteins, Wings, Animal, Original Article, Neoplasm Invasiveness, Neoplasm Metastasis, Transcription Factors
Cell Death, MAP Kinase Signaling System, Proto-Oncogene Proteins pp60(c-src), JNK Mitogen-Activated Protein Kinases, Enzyme Activation, Drosophila melanogaster, Cell Movement, Neoplasms, Ubiquitin-Conjugating Enzymes, ras Proteins, Animals, Drosophila Proteins, Wings, Animal, Original Article, Neoplasm Invasiveness, Neoplasm Metastasis, Transcription Factors
46 Research products, page 1 of 5
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
- 5
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).52 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
