Figure 9. Overview of the Anti-Sterol targets activated by TERE1/vitamin K-2 in C81 LnCaP cells.

TERE1 activates SXR target genes (indicated by stars) that hydroxylate cholesterol (CYP7A1, CYP7B1, CYP27A1) to form oxysterol efflux forms of cholesterol, and activates a panel of transporters (ABCA1, ABCB1, ABCG1, SRBI, CD36, APOE, MRP2) that promote cholesterol efflux from the cell. Together these would serve to diminish cholesterol, the major precursor for androgen synthesis. TERE1 also turns on a program of androgen catabolic enzymes with the following activities: CYP3A4 hydroxylates testosterone thus facilitating efflux, SULT2A sulfonates DHT to a form that does not activate the Androgen receptor, HSD17B2 converts Testosterone to estrogen, AKR1C1 catabolizes DHT by reduction to the inactive 3b andostanediol, and UGT2B15 and UGT2B17 glucuronidate the 3a andostanediol catabolite of DHT thus preventing its back conversion to DHT. Overall this suite of TERE1 /K-2/SXR-driven activities executes an anti-sterol program that opposes the CRPC phenotype.