1. β2-Microglobulin Induces Epithelial to Mesenchymal Transition and Confers Cancer Lethality and Bone Metastasis in Human Cancer Cells
- Author
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Majd Zayzafoon, Daqing Wu, Jen Tai Lin, Leland W.K. Chung, Wen-Chin Huang, M. Neale Weizmann, Sajni Josson, Murali Gururajan, Haiyen E. Zhau, and Takeo Nomura
- Subjects
Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,Iron ,Transplantation, Heterologous ,Mice, Nude ,Bone Neoplasms ,Breast Neoplasms ,Biology ,Article ,Metastasis ,Causes of cancer ,Immunocompromised Host ,Mice ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,Hemochromatosis Protein ,Beta-2 microglobulin ,Histocompatibility Antigens Class I ,Membrane Proteins ,Prostatic Neoplasms ,Bone metastasis ,Cancer ,medicine.disease ,Immunohistochemistry ,Kidney Neoplasms ,Transplantation ,Oncology ,Gene Knockdown Techniques ,Cancer cell ,Cancer research ,Female ,beta 2-Microglobulin - 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. Cancer Res; 71(7); 2600–10. ©2011 AACR.
- Published
- 2011
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