GOLM1 promotes prostate cancer progression through activating PI3K-AKT-mTOR signaling.

BACKGROUND

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Various molecular mechanisms account for PCa progression and elucidation of these mechanisms is key for selection of optimal therapies and improvement of patient outcome. Golgi membrane protein 1 (GOLM1) has been identified as a novel biomarker for PCa, but its biological functions and molecular mechanisms remain poorly understood.

METHOD

GOLM1 expression was determined in PCa by tissue microarrays (TMAs) and real-time RT-PCR, Western blot, and immunohistochemistry (IHC) analyses. To investigate GOLM1 functions in vitro and in vivo, we overexpressed and knocked down GOLM1 in PCa cell lines and established xenograft mice models. A series of cytological function assays were used to determine the role of GOLM1 in cell proliferation, migration, invasion, and apoptosis. PI3K-AKT-mTOR signaling pathway downstream of GOLM1 was detected by Western blot and IHC analyses.

RESULT

GOLM1 expression is up-regulated in PCa of all stages and grades. GOLM1 promotes proliferation, migration and invasion, and inhibits apoptosis in PCa cell lines (DU145, PC3, and CWR22Rv1) and xenograft mice models. Moreover, PI3K-AKT-mTOR signaling is positively regulated by GOLM1, whereas PI3 K inhibitor BKM120 significantly abrogates the oncogenic functions of GOLM1.

CONCLUSION

GOLM1 acts as a critical oncogene by promoting PCa cell proliferation, migration and invasion, and inhibiting apoptosis. GOLM1 plays oncogenic functions mainly through activating PI3K-AKT-mTOR signaling pathway. Therefore, agents that block PI3K-AKT-mTOR signaling pathway could be used in PCa patients with GOLM1 up-regulation.