A genome-wide Drosophila epithelial tumorigenesis screen identifies Tetraspanin 29Fb as an evolutionarily conserved suppressor of Ras-driven cancer

Tamara Zoranovic; Jan Manent; Lee Willoughby; Ricardo Matos de Simoes; John E La Marca; Sofya Golenkina; Cuiping Xia; Susanne Gruber; Belinda Angjeli; Elisabeth Eva Kanitz; Shane JF Cronin; G Gregory Neely; Andreas Wernitznig; Patrick O Humbert; Kaylene J Simpson; Constantine S Mitsiades; Helena E Richardson; Josef M Penninger

Journal article

A genome-wide Drosophila epithelial tumorigenesis screen identifies Tetraspanin 29Fb as an evolutionarily conserved suppressor of Ras-driven cancer

Tamara Zoranovic, Jan Manent, Lee Willoughby, Ricardo Matos de Simoes, John E La Marca, Sofya Golenkina, Cuiping Xia, Susanne Gruber, Belinda Angjeli, Elisabeth Eva Kanitz, Shane JF Cronin, G Gregory Neely, Andreas Wernitznig, Patrick O Humbert, Kaylene J Simpson, Constantine S Mitsiades, Helena E Richardson, Josef M Penninger

PLOS GENETICS | PUBLIC LIBRARY SCIENCE | Published : 2018

DOI: 10.1371/journal.pgen.1007688

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Abstract

Oncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, Ras mutations alone are insufficient for tumorigenesis, therefore it is paramount to identify cooperating cancer-relevant signaling pathways. We devised an in vivo near genome-wide, functional screen in Drosophila and discovered multiple novel, evolutionarily-conserved pathways controlling Ras-driven epithelial tumorigenesis. Human gene orthologs of the fly hits were significantly downregulated in thousands of primary tumors, revealing novel prognostic markers for human epithelial tumors. Of the top 100 candidate tumor suppressor genes, 80 were validated in secondary Drosophila assays, identifying many ..

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University of Melbourne Researchers

Helena Richardson Author Anatomy and Physiology

Kaylene Simpson Author Clinical Pathology

Patrick Humbert Author Biochemistry and Pharmacology

Related Projects (1)

Understanding tumour formation driven by the signalling protein Ras

Cancer is a cooperative process, involving mutations in several genes. Activation of the signaling protein, Ras, contributes to ~30% of huma..

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Awarded by Invest NI

Awarded by NHMRC

Awarded by Cancer Council Victoria

Funding Acknowledgements

JMP is supported by IMBA, the Austrian Ministry of Science, ERC Advanced Investigator grant and an Innovator Award from Era of Hope. TZ was supported by a Marie Curie Excellence grant. RdMS is supported by a grant from Invest NI RD0412515. HER and POH were supported by fellowships from the National Health & Medical Research Council (NHMRC). HER was also supported by a La Trobe University bridging fellowship and La Trobe funds. LW, JM, JELM, and SG were supported by a NHMRC grant #1020525 and a PeterMac Foundation grant to HER, JMP, KJS and POH, a Cancer Council Victoria grant #1122083 to HER, POH and JMP and funds from La Trobe Institute of Molecular Science and La Trobe University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.