Hepcidin regulation in prostate and its disruption in prostate cancer

Lia Tesfay, Kathryn A. Clausen, Jin Woo Kim, Poornima Hegde, Xiaohong Wang, Lance D. Miller, Zhiyong Deng, Nicole Blanchette, Tara Arvedson, Cindy K. Miranti, Jodie L. Babitt, Herbert Y. Lin, Donna M. Peehl, Frank M. Torti, Suzy V. Torti

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Hepcidin is a circulating peptide hormone made by the liver that is a central regulator of systemic iron uptake and recycling. Here, we report that prostate epithelial cells also synthesize hepcidin, and that synthesis and secretion of hepcidin are markedly increased in prostate cancer cells and tissue. Prostatic hepcidin functions as an autocrine hormone, decreasing cell surface ferroportin, an iron exporter, increasing intracellular iron retention, and promoting prostate cancer cell survival. Synthesis of hepcidin in prostate cancer is controlled by a unique intersection of pathways that involves BMP4/7, IL6, Wnt, and the dual BMP and Wnt antagonist, SOSTDC1. Epigenetic silencing of SOSTDC1 through methylation is increased in prostate cancer and is associated with accelerated disease progression in patients with prostate cancer. These results establish a new connection between iron metabolism and prostate cancer, and suggest that prostatic dysregulation of hepcidin contributes to prostate cancer growth and progression.

Original languageEnglish (US)
Pages (from-to)2254-2263
Number of pages10
JournalCancer Research
Volume75
Issue number11
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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