Molecular and Cellular Pathobiology b2-Microglobulin Induces Epithelial to Mesenchymal Transition and Confers Cancer Lethality and Bone Metastasis in Human Cancer Cells

نویسندگان

  • Sajni Josson
  • Takeo Nomura
  • Jen-Tai Lin
  • Wen-Chin Huang
  • Daqing Wu
  • Haiyen E. Zhau
  • Majd Zayzafoon
  • M. Neale Weizmann
  • Murali Gururajan
  • Leland W. K. Chung
چکیده

Bone metastasis is one of the predominant causes of cancer lethality. This study demonstrates for the first time how b2-microglobulin (b2-M) supports lethal metastasis in vivo in human prostate, breast, lung, and renal cancer cells. b2-M mediates this process by activating epithelial to mesenchymal transition (EMT) to promote lethal bone and soft tissue metastases in host mice. b2-M interacts with its receptor, hemochromatosis (HFE) protein, to modulate iron responsive pathways in cancer cells. Inhibition of either b2-M or HFE results in reversion of EMT. These results demonstrate the role of b2-M in cancer metastasis and lethality. Thus, b2-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.

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β2-microglobulin induces epithelial to mesenchymal transition and confers cancer lethality and bone metastasis in human cancer cells.

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تاریخ انتشار 2011