RRC ID 28902
著者 Ilanges A, Jahanshahi M, Balobin DM, Pfleger CM.
タイトル Alcohol interacts with genetic alteration of the Hippo tumor suppressor pathway to modulate tissue growth in Drosophila.
ジャーナル PLoS One
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.
巻・号 8(10)
ページ e78880
公開日 2013-10-21
DOI 10.1371/journal.pone.0078880
PII PONE-D-13-15722
PMID 24205337
PMC PMC3804493
MeSH Animals Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / drug effects* Drosophila melanogaster / genetics* Drosophila melanogaster / physiology Ethanol / pharmacology* Intracellular Signaling Peptides and Proteins / metabolism* Phenotype Protein Serine-Threonine Kinases / metabolism* Signal Transduction / drug effects Signal Transduction / genetics Stress, Physiological / drug effects Tumor Suppressor Proteins / metabolism*
IF 2.74
引用数 6
WOS 分野 CELL BIOLOGY
リソース情報
ショウジョウバエ 12072R-2 4005R-2