Journal article

Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue

Carole LC Poon, Anthony M Brumby, Helena E Richardson

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | MDPI | Published : 2018

Abstract

The Ras oncogene (Rat Sarcoma oncogene, a small GTPase) is a key driver of human cancer, however alone it is insufficient to produce malignancy, due to the induction of cell cycle arrest or senescence. In a Drosophila melanogaster genetic screen for genes that cooperate with oncogenic Ras (bearing the RasV12 mutation, or RasACT), we identified the Drosophila Src (Sarcoma virus oncogene) family non-receptor tyrosine protein kinase genes, Src42A and Src64B, as promoting increased hyperplasia in a whole epithelial tissue context in the Drosophila eye. Moreover, overexpression of Src cooperated with RasACT in epithelial cell clones to drive neoplastic tumourigenesis. We found that Src overexpres..

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University of Melbourne Researchers

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Funding Acknowledgements

We thank all members of the lab for help and advice, and Peter Burke for maintaining the fly stocks. Thanks to Kathryn Guthridge, Leonie Quinn, Linda Parsons, Patrick Humbert and Geraldine O'Neill (The Children's Hospital Westmead, Sydney) for useful discussions on the results and interpretations. We acknowledge Sarah Ellis and the Microscope Core Facility, Peter MacCallum Cancer Centre and Simon Crawford at the Department of Botany, University of Melbourne for assistance with the SEM images. We are appreciative to the fly community for supplying reagents and Flybase for their wealth of information. This work was supported by NIH-R21 grant (1R21CA098997-01) to H.E.R., and a Wellcome Trust Senior Research Fellowship and National Health and Medical Research Council (NHMRC) Fellowships to H.E.R. (#299842, #454700), as well as funds from the Peter MacCallum Cancer Centre and La Trobe Institute of Molecular Science and La Trobe University to H.E.R. A.M.B. was supported by an NIH-R21 grant (1R21CA098997-01) and an NHMRC grant (#350396). C.L.C.P. was supported by a Melbourne Research Scholarship from the University of Melbourne and currently by an NHMRC grant (#1142469).