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Interaction between RasV12 and scribbled clones induces tumour growth and invasion

A Corrigendum to this article was published on 15 February 2017

This article has been updated


Human tumours have a large degree of cellular and genetic heterogeneity1. Complex cell interactions in the tumour and its microenvironment are thought to have an important role in tumorigenesis and cancer progression2. Furthermore, cooperation between oncogenic genetic lesions is required for tumour development3; 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 mutations4, 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 RasV12 (ref. 5) and loss-of-function mutations in the conserved tumour suppressor scribbled (scrib)6,7 gives rise to metastatic tumours that display many characteristics observed in human cancers8,9,10,11. Here we show that clones of cells bearing different mutations can cooperate to promote tumour growth and invasion in Drosophila. We found that the RasV12 and scrib- mutations can also cause tumours when they affect different adjacent epithelial cells. We show that this interaction between RasV12 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 RasV12 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.

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Figure 1: Interclonal cooperation between Ras V12 and scrib - causes tumours.
Figure 2: Synergy between Ras and JAK/STAT signalling promotes growth and invasion in RasV12scrib- and RasV12 //scrib- tumours.
Figure 3: JNK signalling drives oncogenic cooperation upstream of JAK/STAT.
Figure 4: Tissue damage, compensatory growth and a model for interclonal oncogenic cooperation.

Change history

  • 15 February 2017

    Nature 463, 545–548 (2010); doi:10.1038/nature08702 In this Letter, Fig. 2h was inadvertently a duplicate of Fig. 2m, owing to figure reformatting after the manuscript had been accepted. The correct image for the Upd//+ experiment in Fig. 2h is shown in Fig. 1 of this Corrigendum. This error does not affect the results or conclusions of the Letter, and we apologize for the mistake.


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We thank E. Bach, D. Harrison, J. Castelli-Gair Hombria, M. Zeidler, T. Adachi-Yamada, M. Mlodzik, E. Matunis, D. Montell, H. Agaisse, the Bloomington Stock Center and the National Institute of Genetics (Kyoto) for fly strains, and T. Ni, S. Landrette and M. Rojas for comments. R. Pagliarini and S. Landrette helped with microarray analysis and RT–PCR. We thank T. Igaki for discussing the manuscript and providing FRT82B,tub-Gal80,scrib1 /TM6B flies. M.W. is a Yale predoctoral fellow. J.C.P.-P. was funded by a Spanish Ministry of Education postdoctoral fellowship. This work was supported by a grant from NIH/NCI to T.X. T.X. is a Howard Hughes Medical Institute Investigator.

Author Contributions M.W., J.C.P.-P. and T.X. designed research, M.W. and J.C.P.-P. performed experiments and analysed the data. M.W., J.C.P.-P. and T.X. wrote the manuscript.

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Correspondence to Tian Xu.

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Wu, M., Pastor-Pareja, J. & Xu, T. Interaction between RasV12 and scribbled clones induces tumour growth and invasion. Nature 463, 545–548 (2010).

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