WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth.
Cell Rep
; 17(8): 1962-1977, 2016 11 15.
Article
in En
| MEDLINE
| ID: mdl-27851961
ABSTRACT
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 ß-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoproteins
/
Neoplastic Stem Cells
/
Disease Progression
/
Cytoskeletal Proteins
/
Intracellular Signaling Peptides and Proteins
/
Adaptor Proteins, Signal Transducing
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2016
Type:
Article