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dc.contributor.authorManent, J
dc.contributor.authorBanerjee, S
dc.contributor.authorde Matos Simoes, R
dc.contributor.authorZoranovic, T
dc.contributor.authorMitsiades, C
dc.contributor.authorPenninger, JM
dc.contributor.authorSimpson, KJ
dc.contributor.authorHumbert, PO
dc.contributor.authorRichardson, HE
dc.date.accessioned2021-02-04T01:39:34Z
dc.date.available2021-02-04T01:39:34Z
dc.date.issued2017-10-05
dc.identifierpii: onc2017175
dc.identifier.citationManent, J., Banerjee, S., de Matos Simoes, R., Zoranovic, T., Mitsiades, C., Penninger, J. M., Simpson, K. J., Humbert, P. O. & Richardson, H. E. (2017). Autophagy suppresses Ras-driven epithelial tumourigenesis by limiting the accumulation of reactive oxygen species. ONCOGENE, 36 (40), pp.5576-5592. https://doi.org/10.1038/onc.2017.175.
dc.identifier.issn0950-9232
dc.identifier.urihttp://hdl.handle.net/11343/259435
dc.description.abstractActivation of Ras signalling occurs in ~30% of human cancers; however, activated Ras alone is not sufficient for tumourigenesis. In a screen for tumour suppressors that cooperate with oncogenic Ras (RasV12) in Drosophila, we identified genes involved in the autophagy pathway. Bioinformatic analysis of human tumours revealed that several core autophagy genes, including GABARAP, correlate with oncogenic KRAS mutations and poor prognosis in human pancreatic cancer, supporting a potential tumour-suppressive effect of the pathway in Ras-driven human cancers. In Drosophila, we demonstrate that blocking autophagy at any step of the pathway enhances RasV12-driven epithelial tissue overgrowth via the accumulation of reactive oxygen species and activation of the Jun kinase stress response pathway. Blocking autophagy in RasV12 clones also results in non-cell-autonomous effects with autophagy, cell proliferation and caspase activation induced in adjacent wild-type cells. Our study has implications for understanding the interplay between perturbations in Ras signalling and autophagy in tumourigenesis, which might inform the development of novel therapeutics targeting Ras-driven cancers.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleAutophagy suppresses Ras-driven epithelial tumourigenesis by limiting the accumulation of reactive oxygen species
dc.typeJournal Article
dc.identifier.doi10.1038/onc.2017.175
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleOncogene
melbourne.source.volume36
melbourne.source.issue40
melbourne.source.pages5576-5592
melbourne.identifier.nhmrc1020525
dc.rights.licenseCC BY
melbourne.elementsid1214510
melbourne.contributor.authorHumbert, Patrick
melbourne.contributor.authorSimpson, Kaylene
melbourne.contributor.authorRichardson, Helena
dc.identifier.eissn1476-5594
melbourne.identifier.fundernameidNHMRC, 1020525
melbourne.accessrightsOpen Access


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