title: Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation.
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.
authors: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.
authors: Zhimin
authors: Z
authors: Gu
authors: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.
authors: He
authors: H
authors: Wang
authors: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.
authors: Jiliang
authors: J
authors: Xia
authors: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.
authors: Ye
authors: Y
authors: Yang
authors: Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa.
authors: Zhendong
authors: Z
authors: Jin
authors: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.
authors: Hongwei
authors: H
authors: Xu
authors: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Jumei
authors: J
authors: Shi
authors: Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
authors: Ivana
authors: I
authors: De Domenico
authors: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa. fenghuang-zhan@uiowa.edu guido-tricot@uiowa.edu.
authors: Guido
authors: G
authors: Tricot
authors: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa. fenghuang-zhan@uiowa.edu guido-tricot@uiowa.edu.
authors: Fenghuang
authors: F
authors: Zhan
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001862:Bone Resorption / Q000235:genetics / Q000473:pathology; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007501:Iron / Q000378:metabolism*; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000096:biosynthesis; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D011990:Receptors, Transferrin / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D000098742:Ferroportin
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D027682:Cation Transport Proteins; D016328:NF-kappa B; D011990:Receptors, Transferrin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000098742:Ferroportin; D007501:Iron