Journal
CANCER RESEARCH
Volume 71, Issue 7, Pages 2600-2610Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-10-3382
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Funding
- [P01-CA98912]
- [DAMD-17-03-02-0033]
- [RO1-CA122602]
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Bone metastasis is one of the predominant causes of cancer lethality. This study demonstrates for the first time how beta 2-microglobulin (beta 2-M) supports lethal metastasis in vivo in human prostate, breast, lung, and renal cancer cells. beta 2-M mediates this process by activating epithelial to mesenchymal transition (EMT) to promote lethal bone and soft tissue metastases in host mice. beta 2-M interacts with its receptor, hemochromatosis (HFE) protein, to modulate iron responsive pathways in cancer cells. Inhibition of either beta 2-M or HFE results in reversion of EMT. These results demonstrate the role of beta 2-M in cancer metastasis and lethality. Thus, beta 2-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. (C)2011 AACR.
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