β2-microglobulin induces epithelial to mesenchymal transition and confers cancer lethality and bone metastasis in human cancer cells.
β2-microglobulin induces epithelial to mesenchymal transition and confers cancer lethality and bone metastasis in human cancer cells.
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DOI：
10.1158/0008-5472.can-10-3382
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发表时间：
2011-04-01
期刊：
影响因子：
11.2
通讯作者：
Chung LW
中科院分区：
文献类型：
--
作者：
Josson S;Nomura T;Lin JT;Huang WC;Wu D;Zhau HE;Zayzafoon M;Weizmann MN;Gururajan M;Chung LW
骨转移是导致癌症死亡的主要原因之一。本研究首次证实了β2-微球蛋白（β2-M）在人前列腺癌、乳腺癌、肺癌和肾癌细胞体内支持致死性转移的机制。在宿主小鼠中，β2-M通过激活上皮细胞到间充质细胞的转化（EMT）来促进致死性骨和软组织转移，从而介导这一过程。β2-M与其受体血色素沉着症（HFE）蛋白相互作用，调节癌细胞中的铁反应途径。抑制β2-M或HFE均可导致EMT的逆转。这些结果表明β2-M在肿瘤转移和致死性中的作用。因此，β2-M及其下游信号通路是癌症转移的预后标志物和癌症治疗的新靶点。
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.