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Description

Homeobox protein Hox-B13 (UniProt Q92826) is encoded by the HOXB13 (also known as PSGD) gene (Gene ID 10481) in human. HOXB13 is a homeobox gene family member whose expression is restricted to prostate tissues and is highly correlated with that of androgen receptor (AR). Hox-B13 suppresses androgen-stimulated AR activity via direct AR interaction and thereby inhibits androgen-dependent (AD) prostate cancer (PCa) growth under androgen-rich conditions. On the other hand, HOXB13 is also known to be over-expressed in castration-resistant PCa (CRPC), where it plays a dichotomic role in promoting androgen-independent (AI) PCa growth. The zinc level in human prostate is markedly diminished in prostatic epithelial tumors and continues to decline during progression towards AI growth. HOXB13 over-expression upregulates transcription of its target genes SLC30A10 (ZnT10) and SLC30A4 (ZnT4) for zinc output transporters, which are responsible for the reduction in zinc level in CRPC. The diminished intracellular zinc level in turn stimulates NF-kappaB signaling and promotes invasion and metastasis of CRPC cells.