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Mol Cell Biol. 2011 Oct;31(19):4036-51. doi: 10.1128/MCB.01342-10. Epub 2011 Jul 11.

A pathway for the control of anoikis sensitivity by E-cadherin and epithelial-to-mesenchymal transition.

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  • 1Department of Biochemistry and Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506, USA.


Detachment of epithelial cells from matrix or attachment to an inappropriate matrix engages an apoptotic response known as anoikis, which prevents metastasis. Cellular sensitivity to anoikis is compromised during the oncogenic epithelial-to-mesenchymal transition (EMT), through unknown mechanisms. We report here a pathway through which EMT confers anoikis resistance. NRAGE (neurotrophin receptor-interacting melanoma antigen) interacted with a component of the E-cadherin complex, ankyrin-G, maintaining NRAGE in the cytoplasm. Oncogenic EMT downregulated ankyrin-G, enhancing the nuclear localization of NRAGE. The oncogenic transcriptional repressor protein TBX2 interacted with NRAGE, repressing the tumor suppressor gene p14ARF. P14ARF sensitized cells to anoikis; conversely, the TBX2/NRAGE complex protected cells against anoikis by downregulating this gene. This represents a novel pathway for the regulation of anoikis by EMT and E-cadherin.

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