GPR39 Overexpression in OSCC Promotes YAP-Sustained Malignant Progression
1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Journal of Dental Research
|April 24, 2020
Summary
Oral squamous cell carcinoma (OSCC) growth is driven by YAP. We found GPR39 receptor overexpression correlates with YAP activity, poor survival, and malignant progression in OSCC, suggesting GPR39 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Clinical outcomes for oral squamous cell carcinoma (OSCC) remain poor due to limited targeted therapies.
- YAP, a transcriptional coactivator, is crucial in OSCC malignant progression, but targeting YAP or the Hippo pathway is challenging.
- Identifying upstream regulators of YAP is essential for novel therapeutic strategies in YAP-driven cancers.
Purpose of the Study:
- To investigate YAP's role in OSCC and identify its upstream regulators.
- To explore the potential of GPR39 as a therapeutic target and biomarker in OSCC.
Main Methods:
- Assessed YAP overactivation and its correlation with OSCC progression and survival.
- Examined GPR39 expression in OSCC and its relationship with YAP activity.
- Investigated the signaling pathway (Gαq/11-RhoA) linking GPR39 to YAP.
- Evaluated the effect of GPR39 inhibition on OSCC growth.
Main Results:
- YAP was found to be overactivated in OSCC, with high YAP activity linked to poor survival and malignant progression.
- GPR39 was overexpressed in OSCC, and its expression correlated with YAP activity.
- High GPR39 expression was associated with malignant progression and poor survival in OSCC patients.
- GPR39 was shown to regulate YAP via a Gαq/11-RhoA-dependent pathway.
- Inhibiting GPR39 effectively suppressed YAP-sustained OSCC growth.
Conclusions:
- GPR39 is overexpressed in OSCC and promotes malignant progression by regulating YAP activity through the Gαq/11-RhoA pathway.
- GPR39 represents a promising therapeutic target for OSCC.
- GPR39 can serve as a predictive biomarker for OSCC treatment strategies.
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