biostudies-literatureKumar SNCRR NIH HHSNCI NIH HHSNIGMS NIH HHS4036-51https://www.ebi.ac.uk/biostudies/studies/S-EPMC3187352biostudies-literatureUnknown31(19)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.Molecular and cellular biologyA pathway for the control of anoikis sensitivity by E-cadherin and epithelial-to-mesenchymal transition.PMC3187352RR020866P20 RR016440S10 RR020866P30 GM103488P20 RR16440R01 CA123359R01CA123359Schupp JZhang FCieply BKilliam EFrisch SMPark SHRimm DLKumar SfalseA pathway for the control of anoikis sensitivity by E-cadherin and epithelial-to-mesenchymal transition.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.2011-01-01T00:00:00Z2011 Oct2024-10-18T03:59:45.453Z2019-03-27T00:44:37ZS-EPMC31873522174688110.1128/MCB.01342-1010.1128/mcb.01342-10