Journal
CELL REPORTS
Volume 17, Issue 8, Pages 1962-1977Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.10.064
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Funding
- Spanish Ministry of Science and Innovation (MICINN)
- MINECO [SAF2013-45937-R]
- MINECO/FEDER [SAF2015-70368-R]
- European Union [EU-FP7-2009-CT222887]
- Instituto de Salud Carlos III Centro de Investigacion Biomedica en Red (CIBERNED)
- ISCIII-RETIC [RD12/0036/0009]
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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 beta-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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