WWTR1
Overview
WWTR1 (also known as TAZ) encodes a transcriptional coactivator that, together with YAP1, relays mechanical and growth factor signals to TEAD transcription factors as part of the Hippo pathway. In gallbladder cancer, WWTR1 is required alongside YAP1 for stiffness-induced SEMA7A transcription in cancer-associated fibroblasts.
Alterations observed in the corpus
- WWTR1 (TAZ) siRNA abolished stiffness-induced gallbladder fibroblast activation and SEMA7A secretion in primary human GF cultures on 16 kPa hydrogels; acts in concert with YAP1 as a mechanotransducer upstream of TEAD1/SEMA7A. PMID:24997986
- WWTR1 (TAZ) is not mutated in uRCC but its nuclear accumulation (with YAP1) marks the NF2-loss subset and is driven by loss of NF2-mediated Hippo pathway suppression; shYAP1 knockdown reverses proliferation and colony-formation phenotypes in NF2-loss nccRCC lines. PMID:27713405
Cancer types (linked)
- Gallbladder cancer (GBC): WWTR1 is a mechanotransducer in the stiff desmoplastic stroma driving SEMA7A-mediated paracrine tumor promotion. PMID:24997986
Co-occurrence and mutual exclusivity
- Functions cooperatively with YAP1 upstream of TEAD1 to drive SEMA7A expression under mechanical stress; verteporfin (YAP/TAZ inhibitor) blocks both YAP1 and WWTR1 activity. PMID:24997986
Therapeutic relevance
- Verteporfin abolishes WWTR1/YAP1-driven SEMA7A induction in GFs and downstream GBC tumor-promoting effects; provides rationale for YAP/TAZ inhibition as a stromal-targeting strategy. PMID:24997986
Open questions
- Relative contributions of WWTR1 vs YAP1 to SEMA7A transcription are not individually quantified; whether WWTR1 somatic mutations occur in GBC was not examined in this study.
Sources
This page was processed by entity-page-writer on 2026-05-15. - PMID:27713405
This page was processed by entity-page-writer on 2026-05-15.