GNA13 Induces Fibroblast Transformation and Promotes Malignant Progression of Head and Neck Squamous Cell Carcinoma by Tumor Cell-Derived Exosomes

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is associated with a substantial incidence and metastasis rate. G protein subunit alpha 13 (GNA13), a member of the G protein family, is closely associated with the development of multiple tumors. We intended to explore the function and mechanism of GNA13 on the malignant phenotype of HNSCC. Methods: The biological effects of GNA13 on HNSCC cells were analyzed by immunoblotting and PCR. The effects of GNA13 on fibroblast activity under the action of exosomes were investigated by isolating exosomes from HNSCC cells and co-culturing them with fibroblasts. The molecular pathway by which GNA13 regulates the miR-26a-5p/STE20-related adaptor beta (STRADB) axis through exosomes on fibroblasts was confirmed by in vitro experiments. The influence that fibroblasts overexpressing STRADB have a malignant phenotype on HNSCC cells was confirmed using a co-culture system. The promotion of cancer cell growth in nude mice by GNA13 was verified by in vivo experiments. Results: GNA13 was found to be an independent prognostic factor regulating the growth of HNSCC. GNA13 induced fibroblast transformation and promoted its growth and migratory activity through exosomal regulation of the miR-26a-5p/STRADB axis. Meanwhile, fibroblasts overexpressing STRADB reversed the effect of GNA13 deletion upon the malignant phenotype of HNSCC cells. Conclusions: GNA13, as a key gene, significantly affects the malignant phenotype of HNSCC and influences fibroblast activity via the exosome/miR-26a-5p/STRADB axis, further altering the microenvironment in which the tumor resides. GNA13 may be a promising prognostic biomarker among patients with HNSCC.