YAP1 mediates gastric adenocarcinoma peritoneal metastases that are attenuated by YAP1 inhibition
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View abstract on PubMed
Summary
This summary is machine-generated.Yes-associated protein 1 (YAP1) drives peritoneal carcinomatosis (PC) in advanced gastric cancer. Inhibiting YAP1 suppressed tumor growth and eliminated PC, suggesting YAP1 as a therapeutic target for these patients.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Metastasis
Background
- Peritoneal carcinomatosis (PC) affects ~45% of advanced gastric adenocarcinoma (GAC) patients, correlating with poor survival.
- The molecular mechanisms driving PC remain largely unknown.
- The role of the yes-associated protein 1 (YAP1) oncogene in PC is unclear.
Purpose Of The Study
- Investigate the function of YAP1 in peritoneal carcinomatosis (PC).
- Determine YAP1's potential as a therapeutic target for advanced gastric adenocarcinoma (GAC) with PC.
Main Methods
- Utilized patient-derived PC cells, xenografts (PDX), and orthotopic models (PDO).
- Employed immunofluorescence, immunohistochemistry, RNA sequencing (RNA-Seq), and single-cell RNA-Seq (sc-RNA-Seq).
- Performed YAP1 knockout and inhibition studies to assess its role in metastasis.
Main Results
- YAP1 was highly upregulated in PC cells, promoting cancer stem cell (CSC) properties and metastasis.
- YAP1-high PC cells exhibited CSC characteristics and readily formed tumors in vivo.
- Genetic YAP1 knockout significantly reduced tumor growth and eradicated PC in a PDO model.
- Pharmacologic YAP1 inhibition decreased CSC properties and suppressed tumor growth, particularly in combination with cytotoxics.
Conclusions
- YAP1 is crucial for the development of PC.
- YAP1 inhibition effectively attenuates PC.
- Targeting YAP1 presents a promising therapeutic strategy for GAC patients with PC.
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