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• W3036667074 endingPage "4465" @default.
• W3036667074 startingPage "4465" @default.
• W3036667074 abstract "The Target of Rapamycin complex 1 (TORC1) is an evolutionarily conserved kinase complex coordinating cellular growth with nutritional conditions and growth factor signaling, and its activity is elevated in many cancer types. The use of TORC1 inhibitors as anticancer drugs is, however, limited by unwanted side-effects and development of resistance. We therefore attempted to identify limiting modulators or downstream effectors of TORC1 that could serve as therapeutic targets. Drosophila epithelial tissues that lack the tumor suppressor Pten hyperproliferate upon nutrient restriction in a TORC1-dependent manner. We probed candidates of the TORC1 signaling network for factors limiting the overgrowth of Pten mutant tissues. The serine/arginine-rich splicing factor 2 (SF2) was identified as the most limiting factor: SF2 knockdown drives Pten mutant cells into apoptosis, while not affecting control tissue. SF2 acts downstream of or in parallel to TORC1 but is not required for the activation of the TORC1 target S6K. Transcriptomics analysis revealed transcripts with alternatively used exons regulated by SF2 in the tumor context, including p53. SF2 may therefore represent a highly specific therapeutic target for tumors with hyperactive TORC1 signaling." @default.
• W3036667074 created "2020-06-25" @default.
• W3036667074 creator A5069902765 @default.
• W3036667074 creator A5071543412 @default.
• W3036667074 date "2020-06-24" @default.
• W3036667074 modified "2023-10-08" @default.
• W3036667074 title "The Splicing Factor SF2 Is Critical for Hyperproliferation and Survival in a TORC1-Dependent Model of Early Tumorigenesis in Drosophila" @default.
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• W3036667074 doi "https://doi.org/10.3390/ijms21124465" @default.
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• W3036667074 hasPublicationYear "2020" @default.
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