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

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

Research output: Contribution to journalArticle

80 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2600-2610
Number of pages11
JournalCancer Research
Volume71
Issue number7
DOIs
StatePublished - Apr 1 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Josson, S., Nomura, T., Lin, J. T., Huang, W. C., Wu, D., Zhau, H. E., Zayzafoon, M., Neale Weizmann, M., Gururajan, M., & Chung, L. W. K. (2011). β2-microglobulin induces epithelial to mesenchymal transition and confers cancer lethality and bone metastasis in human cancer cells. Cancer Research, 71(7), 2600-2610. https://doi.org/10.1158/0008-5472.CAN-10-3382