Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation

Zhimin Gu; He Wang; Jiliang Xia; Ye Yang; Zhendong Jin; Hongwei Xu; Jumei Shi; Ivana De Domenico; Guido Tricot; Fenghuang Zhan

doi:10.1158/0008-5472.CAN-14-3804

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Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation

Journal article

Open access

Peer reviewed

Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation

Zhimin Gu, He Wang, Jiliang Xia, Ye Yang, Zhendong Jin, Hongwei Xu, Jumei Shi, Ivana De Domenico, Guido Tricot and Fenghuang Zhan

Cancer research (Chicago, Ill.), Vol.75(11), pp.2211-2221

06/01/2015

DOI: 10.1158/0008-5472.CAN-14-3804

PMCID: PMC4946247

PMID: 25855377

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Abstract

Iron homeostasis is disrupted in multiple myeloma, a difficult-to-cure plasma cell malignancy with lytic bone lesions. Here, we systematically analyzed iron gene expression signature and demonstrated that mRNA expression of iron exporter ferroportin (FPN1) is significantly downregulated in myeloma cells and correlates negatively with clinic outcome. Restoring expression of FPN1 reduces intracellular liable iron pool, inhibits STAT3-MCL-1 signaling, and suppresses myeloma cells growth. Furthermore, we demonstrated that mRNA of FPN1 is also downregulated at the initial stages of osteoclast differentiation and suppresses myeloma cell-induced osteoclast differentiation through regulating iron regulator TFRC, NF-κB, and JNK pathways. Altogether, we demonstrated that downregulation of FPN1 plays critical roles in promoting myeloma cell growth and bone resorption in multiple myeloma.

Animals

Antigens, CD - biosynthesis

Bone Resorption - genetics

Bone Resorption - pathology

Cation Transport Proteins - biosynthesis

Cation Transport Proteins - genetics

Cell Differentiation

Cell Line, Tumor

Cell Proliferation - genetics

Gene Expression Regulation, Neoplastic

Humans

Iron - metabolism

Mice

Multiple Myeloma - genetics

Multiple Myeloma - metabolism

Multiple Myeloma - pathology

NF-kappa B - biosynthesis

Osteoclasts - metabolism

Osteoclasts - pathology

Receptors, Transferrin - biosynthesis

Signal Transduction - genetics

STAT3 Transcription Factor - biosynthesis

Details

Title: Subtitle: Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation
Creators: Zhimin Gu - University of Iowa
He Wang - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa
Jiliang Xia - University of Iowa
Ye Yang - University of Iowa
Zhendong Jin - University of Iowa
Hongwei Xu - University of Iowa
Jumei Shi - Tongji University
Ivana De Domenico - University of Utah
Guido Tricot - University of Iowa
Fenghuang Zhan - University of Iowa
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.75(11), pp.2211-2221
DOI: 10.1158/0008-5472.CAN-14-3804
PMID: 25855377
PMCID: PMC4946247
NLM abbreviation: Cancer Res
ISSN: 0008-5472
eISSN: 1538-7445
Grant note: R01 CA152105 / NCI NIH HHS R01 CA115399 / NCI NIH HHS R01CA115399 / NCI NIH HHS R21 CA143887 / NCI NIH HHS R01CA152105 / NCI NIH HHS R21CA143887 / NCI NIH HHS P30CA086862 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 06/01/2015
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry; Internal Medicine
Record Identifier: 9984366017802771

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