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?2-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 ?2-microglobulin (?2-M) supports lethal metastasis in vivo in human prostate, breast, lung, and renal cancer cells. ?2-M mediates this process by activating epithelial to mesenchymal transition (EMT) to promote lethal bone and soft tissue metastases in host mice. ?2-M interacts with its receptor, hemochromatosis (HFE) protein, to modulate iron responsive pathways in cancer cells. Inhibition of either ?2-M or HFE results in reversion of EMT. These results demonstrate the role of ?2-M in cancer metastasis and lethality. Thus, ?2-M and its downstream signaling pathways are promising prognostic markers of cancer metastases and novel therapeutic targets for cancer therapy.

SUBMITTER: Josson S

PROVIDER: S-EPMC3182156 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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

Josson Sajni S Nomura Takeo T Lin Jen-Tai JT Huang Wen-Chin WC Wu Daqing D Zhau Haiyen E HE Zayzafoon Majd M Weizmann M Neale MN Gururajan Murali M Chung Leland W K LW

Cancer research 20110322 7

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. ...[more]

PMID: 21427356

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