Siah2-Dependent Concerted Activity of HIF and FoxA2 Regulates Formation of Neuroendocrine Phenotype and Neuroendocrine Prostate Tumors

Jianfei Qi, Koh Nakayama, Robert Cardiff, Alexander D Borowsky, Karen Kaul, Roy Williams, Stan Krajewski, Dan Mercola, Philip M. Carpenter, David Bowtell, Ze'ev A. Ronai

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

Neuroendocrine (NE) phenotype, seen in >30% of prostate adenocarcinomas (PCa), and NE prostate tumors are implicated in aggressive prostate cancer. Formation of NE prostate tumors in the TRAMP mouse model was suppressed in mice lacking the ubiquitin ligase Siah2, which regulates HIF-1α availability. Cooperation between HIF-1α and FoxA2, a transcription factor expressed in NE tissue, promotes recruitment of p300 to transactivate select HIF-regulated genes, Hes6, Sox9, and Jmjd1a. These HIF-regulated genes are highly expressed in metastatic PCa and required for hypoxia-mediated NE phenotype, metastasis in PCa, and the formation of NE tumors. Tissue-specific expression of FoxA2 combined with Siah2-dependent HIF-1α availability enables a transcriptional program required for NE prostate tumor development and NE phenotype in PCa.

Original languageEnglish (US)
Pages (from-to)23-38
Number of pages16
JournalCancer Cell
Volume18
Issue number1
DOIs
StatePublished - Jul 2010

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Fingerprint Dive into the research topics of 'Siah2-Dependent Concerted Activity of HIF and FoxA2 Regulates Formation of Neuroendocrine Phenotype and Neuroendocrine Prostate Tumors'. Together they form a unique fingerprint.

  • Cite this

    Qi, J., Nakayama, K., Cardiff, R., Borowsky, A. D., Kaul, K., Williams, R., Krajewski, S., Mercola, D., Carpenter, P. M., Bowtell, D., & Ronai, Z. A. (2010). Siah2-Dependent Concerted Activity of HIF and FoxA2 Regulates Formation of Neuroendocrine Phenotype and Neuroendocrine Prostate Tumors. Cancer Cell, 18(1), 23-38. https://doi.org/10.1016/j.ccr.2010.05.024