title: Alcohol interacts with genetic alteration of the Hippo tumor suppressor pathway to modulate tissue growth in Drosophila.
abstract: Alcohol-mediated cancers represent more than 3.5% of cancer-related deaths, yet how alcohol promotes cancer is a major open question. Using Drosophila, we identified novel interactions between dietary ethanol and loss of tumor suppressor components of the Hippo Pathway. The Hippo Pathway suppresses tumors in flies and mammals by inactivating transcriptional co-activator Yorkie, and the spectrum of cancers associated with impaired Hippo signaling overlaps strikingly with those associated with alcohol. Therefore, our findings may implicate loss of Hippo Pathway tumor suppression in alcohol-mediated cancers. Ethanol enhanced overgrowth from loss of the expanded, hippo, or warts tumor suppressors but, surprisingly, not from over-expressing the yorkie oncogene. We propose that in parallel to Yorkie-dependent overgrowth, impairing Hippo signaling in the presence of alcohol may promote overgrowth via additional alcohol-relevant targets. We also identified interactions between alcohol and Hippo Pathway over-activation. We propose that exceeding certain thresholds of alcohol exposure activates Hippo signaling to maintain proper growth control and prevent alcohol-mediated mis-patterning and tissue overgrowth.
authors.affiliation: Department of Oncological Sciences, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America ; Yale University, New Haven, Connecticut, United States of America.
authors.forename: Anoj
authors.initials: A
authors.lastname: Ilanges
authors.forename: Maryam
authors.initials: M
authors.lastname: Jahanshahi
authors.forename: Denis M
authors.initials: DM
authors.lastname: Balobin
authors.forename: Cathie M
authors.initials: CM
authors.lastname: Pfleger
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D000431:Ethanol; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases