YAP acts as an independent prognostic marker and regulates growth and metastasis of gastrointestinal stromal tumors via FBXW7-YAP pathway
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View abstract on PubMed
Summary
This summary is machine-generated.High Yes-associated protein (YAP) expression in gastrointestinal stromal tumors (GISTs) indicates a poorer prognosis and increased recurrence risk. YAP is a potential therapeutic target for GIST patients, especially those with resistance to tyrosine kinase inhibitors.
Area Of Science
- Oncology
- Molecular Biology
- Gastroenterology
Background
- Tyrosine kinase inhibitors (TKIs) improve prognosis for gastrointestinal stromal tumor (GIST) patients but face limited efficacy due to resistance and toxicity.
- Yes-associated protein (YAP), a Hippo pathway coactivator, is implicated in TKI resistance and aggressive GIST phenotypes.
- FBXW7 mediates YAP degradation and its levels predict GIST recurrence and TKI efficacy.
Purpose Of The Study
- To evaluate Yes-associated protein (YAP) as a prognostic marker in GIST patients.
- To elucidate the molecular mechanism of the FBXW7-YAP pathway in GIST cells.
Main Methods
- Immunohistochemical staining of YAP in 167 GIST cases.
- Correlation of YAP expression with clinicopathological features.
- In vitro and in vivo examination of the FBXW7-YAP pathway.
Main Results
- High YAP expression (52.1% of cases) was associated with poorer overall survival (P=0.004) and recurrence-free survival (P=0.003).
- YAP expression is an independent prognostic factor for 5-year survival and recurrence-free survival (P<0.01).
- FBXW7 directly targets YAP, influencing GIST cell proliferation, invasion, and migration; high YAP correlated with FBXW7 deficiency in mouse models.
Conclusions
- YAP expression is a predictive marker for recurrence in GIST patients post-curative resection.
- YAP represents a potential novel therapeutic target for GISTs, warranting further investigation.
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