GOLM1 as a Potential Therapeutic Target Modulates B7-H3 Secretion to Drive Ovarian Cancer Metastasis

INTRODUCTION: This study was aimed at exploring whether the Golgi membrane protein 1 (GOLM1) enhanced ovarian cancer metastasis through B7-H3-dependent way. METHODS: We collected the ovarian cancer patient samples from available databases including GEPIA, starBase, and Protein Altas that have GOLM1 and B7-H3 mRNA and protein expression. Ovarian cancer cell line SKOV3 was purchased. Knockdown GOLM1 and B7-H3 cell lines were obtained through introducing shRNAs by lentivirus package system, while GOLM1 or B7-H3 overexpression cell line was obtained by introducing GOLM1 full-length gene. Furthermore, wound-healing assay and Transwell assay were performed to assess tumor invasion and metastasis abilities; related proteins' expression was quantitated by western blotting, ELISA, and flow cytometry assay. The protein interaction was quantified by co-immunoprecipitation. RESULTS: GOLM1 has the correlative expression pattern with B7-H3 in ovarian cancer through patient sample databases (R = 0.421). GOLM1 knockdown had minimal impact on B7-H3 mRNA synthesis, while downregulated B7-H3 protein expression on tumor membrane and soluble B7-H3 (sB7-H3) level (p < 0.05) through physical interaction, GOLM1 knockdown, significantly reduce tumor invasion and metastasis in vitro (p < 0.05). Moreover, exogenous sB7-H3 significantly rescued this inhibitory effect. Both GOLM1 and B7-H3 knockdown restrained tumor growth and metastasis in immunodeficient mice and prolonged the survival rate. CONCLUSIONS: GOLM1 acts as an initial oncogenic driving gene by promoting ovarian cancer invasion and metastasis through modulating B7-H3 protein maturation and secretion.