Fig. 7.

Schematic diagram showing the critical role of FDPS in normal prostate and prostate cancer and its associated potential mecahnism (s). (i) FDPS is a crucial intermediate enzyme required for cholesterol and sterol biosynthesis. This enzyme catalyzes production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethyl allyl pyrophosphate. Apart from enzyme catalysis, FDPS is involved in posttranslational modifications (protein prenylation) of GTPases. Inactivation of FDPS through interferon disrupts specialized cell membrane-associated microdomains, such as lipid rafts, required for protein and receptor trafficking, cell signaling, and neurotransmission regulation. (ii) FDPS is overexpressed in prostate cancer and associated with tumor recurrence. FDPS also regulates intra-tumoral androgens, which further interferes with ADT therapy in the localized and locally advanced stages of prostate cancer. (iii) Flow diagram describes various mechanisms associated with FDPS overexpression in prostate cancer cells. FDPS may be stimulated by androgens and ectopic overexpression of FDPS resulted in activation of AKT and ERK signaling for sustained proliferative signals, but deactivates STAT1 pathway, disrupting its tumor suppressive function. ZOL potentially inhibits FDPS thereby modulating the prenylation of small GTPases resulting in deactivation of AKT, ERK and STAT signaling in prostate cancer cells.