title: Myeloma cell-derived Runx2 promotes myeloma progression in bone.
abstract: The progression of multiple myeloma (MM) is governed by a network of molecular signals, the majority of which remain to be identified. Recent studies suggest that Runt-related transcription factor 2 (Runx2), a well-known bone-specific transcription factor, is also expressed in solid tumors, where expression promotes both bone metastasis and osteolysis. However, the function of Runx2 in MM remains unknown. The current study demonstrated that (1) Runx2 expression in primary human MM cells is significantly greater than in plasma cells from healthy donors and patients with monoclonal gammopathy of undetermined significance; (2) high levels of Runx2 expression in MM cells are associated with a high-risk population of MM patients; and (3) overexpression of Runx2 in MM cells enhanced tumor growth and disease progression in vivo. Additional studies demonstrated that MM cell-derived Runx2 promotes tumor progression through a mechanism involving the upregulation of Akt/β-catenin/Survivin signaling and enhanced expression of multiple metastatic genes/proteins, as well as the induction of a bone-resident cell-like phenotype in MM cells. Thus, Runx2 expression supports the aggressive phenotype of MM and is correlated with poor prognosis. These data implicate Runx2 expression as a major regulator of MM progression in bone and myeloma bone disease.
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL;
authors: Timothy N
authors: TN
authors: Trotter
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL;
authors: Mei
authors: M
authors: Li
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL; Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, China;
authors: Qianying
authors: Q
authors: Pan
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL;
authors: Deniz
authors: D
authors: Peker
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL;
authors: Patrick D
authors: PD
authors: Rowan
authors: Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, China;
authors: Juan
authors: J
authors: Li
authors: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa;
authors: Fenghuang
authors: F
authors: Zhan
authors: Department of Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, AR; and.
authors: Larry J
authors: LJ
authors: Suva
authors: Comprehensive Cancer Center and the Center for Metabolic Bone Disease, and Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL.
authors: Amjad
authors: A
authors: Javed
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL; Comprehensive Cancer Center and the Center for Metabolic Bone Disease, and.
authors: Yang
authors: Y
authors: Yang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D010014:Osteolysis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; C117749:Birc5 protein, mouse; D050659:Core Binding Factor Alpha 1 Subunit; D051034:Inhibitor of Apoptosis Proteins; C493709:RUNX2 protein, human; D012097:Repressor Proteins; C493716:Runx2 protein, mouse; D000077022:Survivin; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt