期刊
CELL DEATH & DISEASE
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2013.392
关键词
Src42A; invasion; cell death; JNK; Bendless; dUev1a
类别
资金
- National Basic Research Program of China (973 Program) [2010CB944901, 2011CB943903]
- National Natural Science Foundation of China [31071294, 31171413, 31371490]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20120072110023, 20120072120030]
- Shanghai Committee of Science and Technology [09DZ2260100]
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.
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