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The Siah2-HIF-FoxA2 axis in prostate cancer – new markers and therapeutic opportunities.

ABSTRACT: Recent 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-1α 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-1α/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.

SUBMITTER: Qi J

PROVIDER: S-EPMC2964873 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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The Siah2-HIF-FoxA2 axis in prostate cancer – new markers and therapeutic opportunities.

Qi Jianfei J Pellecchia Maurizio M Ronai Ze'ev A ZA

Oncotarget 20100901 5

Recent 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-1α 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 N ...[more]

PMID: 21037926

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Siah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine phenotype and neuroendocrine prostate tumors.

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Siah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine prostate tumors

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DNA Repair Deficiency Is Common in Advanced Prostate Cancer: New Therapeutic Opportunities.

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