title: Hepcidin regulation in prostate and its disruption in prostate cancer.
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.
authors: Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut.
authors: Lia
authors: L
authors: Tesfay
authors: JK Associates, Conshohocken, Pennsylvania.
authors: Kathryn A
authors: KA
authors: Clausen
authors: Panagene Inc., Yuseong-gu, Daejeon, Republic of Korea.
authors: Jin Woo
authors: JW
authors: Kim
authors: Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut.
authors: Poornima
authors: P
authors: Hegde
authors: Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut.
authors: Xiaohong
authors: X
authors: Wang
authors: Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, North Carolina.
authors: Lance D
authors: LD
authors: Miller
authors: Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut.
authors: Zhiyong
authors: Z
authors: Deng
authors: Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut.
authors: Nicole
authors: N
authors: Blanchette
authors: Department of Inflammation, Amgen Inc., Seattle, Washington.
authors: Tara
authors: T
authors: Arvedson
authors: Laboratory of Integrin Signaling, Program in Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan.
authors: Cindy K
authors: CK
authors: Miranti
authors: Program in Anemia Signaling Research, Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Jodie L
authors: JL
authors: Babitt
authors: Program in Anemia Signaling Research, Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Herbert Y
authors: HY
authors: Lin
authors: Department of Urology, Stanford University School of Medicine, Stanford, California.
authors: Donna M
authors: DM
authors: Peehl
authors: Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut.
authors: Frank M
authors: FM
authors: Torti
authors: Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut. storti@uchc.edu.
authors: Suzy V
authors: SV
authors: Torti
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D045744:Cell Line, Tumor; D018450:Disease Progression; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D064451:Hepcidins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007501:Iron / Q000378:metabolism; D008297:Male; D060787:Neoplasm Grading; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D064451:Hepcidins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C480733:SOSTDC1 protein, human; D007501:Iron