[PDF][PDF] WIP drives tumor progression through YAP/TAZ-dependent autonomous cell growth

R Gargini, M Escoll, E García, R García-Escudero… - Cell reports, 2016 - cell.com
R Gargini, M Escoll, E García, R García-Escudero, F Wandosell, IM Antón
Cell reports, 2016cell.com
In cancer, the deregulation of growth signaling pathways drives changes in the cell's
architecture and its environment that allow autonomous growth of tumors. These cells then
acquire a tumor-initiating" stemness" phenotype responsible for disease advancement to
more aggressive stages. Here, we show that high levels of the actin cytoskeleton-associated
protein WIP (WASP-interacting protein) correlates with tumor growth, both of which are
linked to the tumor-initiating cell phenotype. We find that WIP controls tumor growth by …
Summary
In cancer, the deregulation of growth signaling pathways drives changes in the cell's architecture and its environment that allow autonomous growth of tumors. These cells then acquire a tumor-initiating "stemness" phenotype responsible for disease advancement to more aggressive stages. Here, we show that high levels of the actin cytoskeleton-associated protein WIP (WASP-interacting protein) correlates with tumor growth, both of which are linked to the tumor-initiating cell phenotype. We find that WIP controls tumor growth by boosting signals that stabilize the YAP/TAZ complex via a mechanism mediated by the endocytic/endosomal system. When WIP levels are high, the β-catenin Adenomatous polyposis coli (APC)-axin-GSK3 destruction complex is sequestered to the multi-vesicular body compartment, where its capacity to degrade YAP/TAZ is inhibited. YAP/TAZ stability is dependent on Rac, p21-activated kinase (PAK) and mammalian diaphanous-related formin (mDia), and is Hippo independent. This close biochemical relationship indicates an oncogenic role for WIP in the physiology of cancer pathology by increasing YAP/TAZ stability.
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