GOLPH3 promotes prostate adenocarcinoma cell proliferation by enhancing PI3K/AKT/mTOR-associated glucose metabolism.

BACKGROUND

Prostate adenocarcinoma (PRAD) is one of the cancers that threaten the health of male, but its progression mechanism remains unclear. Golgi phosphoprotein 3 (GOLPH3) is aberrantly expressed in many cancers, but its role in PRAD progression remains unknown. This paper aims to study the function of GOLPH3 in PRAD.

METHODS

The online database was used to analyze the expression level of GOLPH3 transcriptome, and the expression level of GOLPH3 protein in PRAD tissues and cells was detected by western blotting. PC-3 and LNCaP cells were selected to construct the GOLPH3 overexpression PRAD cells. CCK8 assay, EdU staining, colony formation assay, and a nude mouse xenograft model were used to evaluate the proliferation of PRAD cells. Glucose metabolism activity was determined by lactate release, intracellular glucose level, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR).

RESULTS

Online public database analysis showed that the expression level of GOLPH3 transcriptome in tumor tissues was significantly higher than that in normal tissues of PRAD patients. And western blotting analysis suggested that GOLPH3 protein expression was elevated in PRAD tissues and cells. Results of CCK8 assay, EdU staining, colony formation assay and nude mouse xenograft analysis showed that GOLPH3 overexpression strongly promoted PRAD cell proliferation in vitro and in vivo. Importantly, GOLPH3 overexpression significantly increased the levels of lactate release and intracellular glucose levels by PRAD cells, and increased glucose metabolism-related enzyme activity, including HK, GPI, PGK, LDHA, and G6PD. Mechanistically, GOLPH3 overexpression markedly increased the p-AKT/AKT and p-mTOR/mTOR ratios, and LY294002 reduced cell proliferation and glucose metabolism levels elevated by GOLPH3 overexpression.

CONCLUSION

GOLPH3, which is overexpressed in PRAD, may enhance glucose metabolic activity in PRAD cells in association with activation of the PI3K/AKT/mTOR pathway, thereby supporting PRAD cell proliferation. These findings provide basic mechanistic evidence for the role of GOLPH3 in PRAD cell metabolism, but further clinical studies are required to determine its prognostic or therapeutic relevance.