fig1

Figure 1. HOXB13 exerts multiple tumor-promoting effects through the regulation of specific target genes. HOXB13 protein can function both as a repressor and activator of transcription. It represses the p21WAF1/CIP1 (p21) tumor suppressor gene, which can block androgen-stimulated cell proliferation and has also been shown to bind directly to the enhancer region of the RFX6 gene, the product of which inhibits the proliferation, migration, and invasion of prostate cancer cells. HOXB13 additionally represses prostate derived Ets factor (PDEF) expression, which in turn blocks the expression of matrix metalloproteinase 9 (MMP-9) and the anti-apoptotic protein survivin, and thus reduces the invasive potential of cells. A further pro-oncogenic effect of HOXB13 is exerted through the upregulation of zinc transporters resulting in lower intracellular zinc concentrations. This reduces the level of inhibitor of NF-κB alpha (IκBα) and promotes NF-κBα signaling leading to increased invasion and metastasis. Right pointing arrows in the nucleus indicate transcription. AR: androgen receptor