title: β2-microglobulin induces epithelial to mesenchymal transition and confers cancer lethality and bone metastasis in human cancer cells.
abstract: Bone metastasis is one of the predominant causes of cancer lethality. This study demonstrates for the first time how β2-microglobulin (β2-M) supports lethal metastasis in vivo in human prostate, breast, lung, and renal cancer cells. β2-M mediates this process by activating epithelial to mesenchymal transition (EMT) to promote lethal bone and soft tissue metastases in host mice. β2-M interacts with its receptor, hemochromatosis (HFE) protein, to modulate iron responsive pathways in cancer cells. Inhibition of either β2-M or HFE results in reversion of EMT. These results demonstrate the role of β2-M in cancer metastasis and lethality. Thus, β2-M and its downstream signaling pathways are promising prognostic markers of cancer metastases and novel therapeutic targets for cancer therapy.
authors.affiliation: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Sajni
authors.initials: S
authors.lastname: Josson
authors.forename: Takeo
authors.initials: T
authors.lastname: Nomura
authors.forename: Jen-Tai
authors.initials: JT
authors.lastname: Lin
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Huang
authors.forename: Daqing
authors.initials: D
authors.lastname: Wu
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
authors.forename: Majd
authors.initials: M
authors.lastname: Zayzafoon
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weizmann
authors.forename: Murali
authors.initials: M
authors.lastname: Gururajan
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000556:secondary*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D001613:beta 2-Microglobulin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D001613:beta 2-Microglobulin; D007501:Iron