Hyperactivated Wnt Signaling Induces Synthetic Lethal Interaction with Rb Inactivation by Elevating TORC1 Activities

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Inactivation of Rb tumor suppressor is common in cancers. Therefore, identification of genes and pathways that are synthetic lethal with Rb will provide new insights into the role of Rb in cancer development and promote the development of novel therapeutic approaches. Here we identified a novel synthetic lethal interaction between Rb inactivation and hyperactivated Wnt signaling and showed that this synthetic lethal interaction is conserved in mammalian systems. We demonstrate that hyperactivated Wnt signaling activate TORC1 activity and induce excessive energy stress with inactivated Rb tumor suppressor, which underpins the evolutionarily conserved synthetic lethal interaction. This study provides novel insights into the interactions between the Rb, Wnt, and mTOR pathways in regulating cellular energy balance, cell growth, and survival.

Vyšlo v časopise: Hyperactivated Wnt Signaling Induces Synthetic Lethal Interaction with Rb Inactivation by Elevating TORC1 Activities. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004357
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004357

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