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Article

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

by 1,2,*,†, 1,3 and 1,2,3,4,*
1
Cell Cycle and Development lab, Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia
2
Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, VIC 3010, Australia
3
Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, VIC 3010, Australia
4
Department of Biochemistry and Genetics, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
*
Authors to whom correspondence should be addressed.
Current address: Sir Peter MacCallum Department of Oncology, University of Melbourne and Cell Growth and Proliferation laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC 3010, Australia.
Int. J. Mol. Sci. 2018, 19(6), 1585; https://doi.org/10.3390/ijms19061585
Received: 19 April 2018 / Revised: 15 May 2018 / Accepted: 23 May 2018 / Published: 27 May 2018
(This article belongs to the Special Issue Drosophila Model and Human Disease)
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 overexpression alone activated the Jun N-terminal Kinase (JNK) signalling pathway to promote actin cytoskeletal and cell polarity defects and drive apoptosis, whereas, in cooperation with RasACT, JNK led to a loss of differentiation and an invasive phenotype. Src + RasACT cooperative tumourigenesis was dependent on JNK as well as Phosphoinositide 3-Kinase (PI3K) signalling, suggesting that targeting these pathways might provide novel therapeutic opportunities in cancers dependent on Src and Ras signalling. View Full-Text
Keywords: Src; Ras; Raf; PTEN; PI3K; cooperative tumourigenesis; Drosophila Src; Ras; Raf; PTEN; PI3K; cooperative tumourigenesis; Drosophila
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MDPI and ACS Style

Poon, C.L.C.; Brumby, A.M.; Richardson, H.E. Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue. Int. J. Mol. Sci. 2018, 19, 1585. https://doi.org/10.3390/ijms19061585

AMA Style

Poon CLC, Brumby AM, Richardson HE. Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue. International Journal of Molecular Sciences. 2018; 19(6):1585. https://doi.org/10.3390/ijms19061585

Chicago/Turabian Style

Poon, Carole L.C., Anthony M. Brumby, and Helena E. Richardson 2018. "Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue" International Journal of Molecular Sciences 19, no. 6: 1585. https://doi.org/10.3390/ijms19061585

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