GPRIN1 enhances gallbladder cancer progression and is associated with the CDK1 pathway

Abstract

Abstract Purpose Recent studies have shown that G protein-regulated inducer of neurite outgrowth 1 (GPRIN1) regulates cancer proliferation and migration. However, there is limited research regarding its role in gallbladder cancer (GBC). We aimed to investigate the mechanism by which GPRIN1 promotes GBC cell proliferation and migration. Methods Immunohistochemistry was performed to visualize in situ GPRIN1 expression in 65 human GBC tissues and 59 corresponding normal tissues. The Kaplan–Meier method was used to analyze the correlation between GPRIN1 and overall survival. Cell proliferation (Celigo and MTT), apoptosis (FACS), and cell migration and invasion assays and a subcutaneous xenograft tumor model were used to define the effects of GPRIN1 downregulation in GBC cells in vitro and in vivo. Coimmunoprecipitation assays, mass spectrometry and Western blotting were performed to identify GPRIN1-interacting proteins. Cell proliferation, MTT and Transwell assays were performed to verify the functional recovery effect of cyclin-dependent protein kinase 1 (CDK1) on GPRIN1. Proteomic analysis of differentially expressed proteins and/or phosphorylated peptides was performed. Results GPRIN1 is upregulated in GBC tumor tissues and high GPRIN1 expression is positively correlated with a poor prognosis in GBC patients. High GPRIN1 expression reinforced the proliferative and invasive capacities of GBC in vitro and in vivo. Coimmunoprecipitation assays, mass spectrometry and Western blotting validated the direct interaction between GPRIN1 and CDK1. Cell proliferation, MTT and Transwell assays suggested that CDK1 exerts a functional recovery effect on GPRIN1. Proteomic analysis revealed the involvement of CDK1 in many biological processes and cellular pathways. Conclusions GPRIN1 promotes the invasion and metastasis of GBC cells via CDK1 pathway activation.

The authors' abstract, as published at the source. Cancer Biology & Therapy, 2026 · DOI ↗