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

This study was aimed at exploring whether the Golgi membrane protein 1 (GOLM1) enhanced ovarian cancer metastasis through B7-H3-dependent way.

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.

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.

GOLM1 acts as an initial oncogenic driving gene by promoting ovarian cancer invasion and metastasis through modulating B7-H3 protein maturation and secretion.