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lüll The Siah2-HIF-FoxA2 axis in prostate cancer - new markers and therapeutic opportunities Qi J; Pellecchia M; Ronai ZAOncotarget 2010[Sep]; 1 (5): 379-85Recent studies indicate the importance of the ubiquitin ligase Siah2 in control of more aggressive prostate tumors - namely, neuroendocrine (NE) prostate tumors and prostate adenocarcinoma (PCa) harboring neuroendocrine lesions. Siah2-dependent expression and activity of HIF-1alpha regulate its availability to form a transcriptional complex with FoxA2, resulting in expression of specific target genes, including Hes6, Sox9 and Jmjd1a, whose co-expression is sufficient for formation of NE tumors and NE lesions in PCa. These studies provide novel markers to diagnose and monitor formation of NE lesions and NE tumors. Furthermore, defining the regulatory axis consisting of Siah2 and HIF-1alpha/FoxA2 cooperation suggests novel therapeutic modalities to treat these most aggressive forms of prostate cancer. Here we review current understanding of Siah role in control of hypoxia and prostate tumor development and highlight potential approaches for targeting components along Siah-regulated pathways.|*Signal Transduction/drug effects[MESH]|Adenocarcinoma/drug therapy/*enzymology/genetics/pathology[MESH]|Animals[MESH]|Antineoplastic Agents/pharmacology[MESH]|Biomarkers, Tumor/*metabolism[MESH]|Drug Design[MESH]|Gene Expression Regulation, Neoplastic[MESH]|Hepatocyte Nuclear Factor 3-beta/*metabolism[MESH]|Humans[MESH]|Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism[MESH]|Male[MESH]|Molecular Targeted Therapy[MESH]|Neuroendocrine Tumors/drug therapy/*enzymology/genetics/pathology[MESH]|Nuclear Proteins/*metabolism[MESH]|Prostatic Neoplasms/drug therapy/*enzymology/genetics/pathology[MESH]|Ubiquitin-Protein Ligases/*metabolism[MESH] |