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Nature. 2010 Jan 28;463(7280):545-8. doi: 10.1038/nature08702. Epub 2010 Jan 13.

Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion.

Author information

1
Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, 295 Congress Avenue, New Haven, Connecticut 06519, USA.

Abstract

Human tumours have a large degree of cellular and genetic heterogeneity. Complex cell interactions in the tumour and its microenvironment are thought to have an important role in tumorigenesis and cancer progression. Furthermore, cooperation between oncogenic genetic lesions is required for tumour development; however, it is not known how cell interactions contribute to oncogenic cooperation. The genetic techniques available in the fruitfly Drosophila melanogaster allow analysis of the behaviour of cells with distinct mutations, making this the ideal model organism with which to study cell interactions and oncogenic cooperation. In Drosophila eye-antennal discs, cooperation between the oncogenic protein Ras(V12) (ref. 5) and loss-of-function mutations in the conserved tumour suppressor scribbled (scrib) gives rise to metastatic tumours that display many characteristics observed in human cancers. Here we show that clones of cells bearing different mutations can cooperate to promote tumour growth and invasion in Drosophila. We found that the Ras(V12) and scrib(-) mutations can also cause tumours when they affect different adjacent epithelial cells. We show that this interaction between Ras(V12) and scrib(-) clones involves JNK signalling propagation and JNK-induced upregulation of JAK/STAT-activating cytokines, a compensatory growth mechanism for tissue homeostasis. The development of Ras(V12) tumours can also be triggered by tissue damage, a stress condition that activates JNK signalling. Given the conservation of the pathways examined here, similar cooperative mechanisms could have a role in the development of human cancers.

PMID:
20072127
PMCID:
PMC2835536
DOI:
10.1038/nature08702
[Indexed for MEDLINE]
Free PMC Article

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