Oncogenic Role of Guanylate Binding Protein 1 in Human Prostate Cancer

The Guanylate binding proteins (GBPs) are a family of large GTPases and the most studied GBP family member is the guanylate binding protein 1 (GBP1). Earlier studies revealed that GBP1 expression was inflammatory cytokines-inducible, and most of the studies focused on inflammation diseases. Increasing number of Cancer studies began to reveal its biological role in cancers recently, although with contradictory findings in literature. It was discovered from our earlier prostate Cancer cell line models studies that when prostate Cancer cells treated with either ethidium bromide or a cell cycle inhibitor flavopiridol for a long-term, the treatment-survived tumor cells experienced metabolic reprogramming toward Warburg effect pathways with greater aggressive features, and one common finding from these cells was the upregulation of GBP1. In this study, possible role of GBP1 in two independent prostate Cancer lines by application of CRISR/Cas9 gene knockout (KO) technology was investigated. The GBP1 gene KO DU145 and PC3 prostate Cancer cells were significantly less aggressive in vitro, with less proliferation, migration, wound healing, and colony formation capabilities, in addition to a significantly lower level of mitochondrial Oxidative Phosphorylation and glycolysis. At the same time, such GBP1 KO cells were significantly more sensitive to chemotherapeutic reagents. Xenograft experiments verified a significantly slower tumor growth of the GBP1 KO cells in nude mouse model. Furthermore, GBP1 protein expression in clinical prostate Cancer sample revealed its aggressive clinical feature correlation and shorter overall survival association. Collectively, our results indicate a pro-survival or oncogenic role of GBP1 in prostate Cancer.

CRISPR/Cas9; energy pathway; guanylate binding protein 1; prostate cancer; xenotransplantation.