GRK3 is a poor prognosticator and serves as a therapeutic target in advanced gastric adenocarcinoma.

ABSTRACT:

Background

G protein-coupled receptor (GPCR) is the most targeted protein family by the FDA-approved drugs. GPCR-kinase 3 (GRK3) is critical for GPCR signaling. Our genomic analysis showed that GRK3 expression correlated with poor prognosis of gastric adenocarcinoma (GAC) patients. However, GRK3's functions and clinical utility in GAC progression and metastases are unknown.

Methods

We studied GRK3 expression in normal, primary, and metastatic GAC tissues. We identified a novel GRK3 inhibitor, LD2, through a chemical-library screen. Through genetic and pharmacologic modulations of GRK3, a series of functional and molecular studies were performed in vitro and in vivo. Impact of GRK3 on YAP1 and its targets was determined.

Results

GRK3 was overexpressed in GAC tissues co

SUBMITTER: Li Y 

PROVIDER: S-EPMC9396876 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature