title: A pathway for the control of anoikis sensitivity by E-cadherin and epithelial-to-mesenchymal transition.
abstract: 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.
authors: Department of Biochemistry and Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506, USA.
authors: Sanjeev
authors: S
authors: Kumar
authors: Sun Hee
authors: SH
authors: Park
authors: Benjamin
authors: B
authors: Cieply
authors: Jane
authors: J
authors: Schupp
authors: Elizabeth
authors: E
authors: Killiam
authors: Fan
authors: F
authors: Zhang
authors: David L
authors: DL
authors: Rimm
authors: Steven M
authors: SM
authors: Frisch
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism; D023102:Anoikis / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins; D000951:Antigens, Neoplasm; D015820:Cadherins; C120897:MAGED1 protein, human; C486541:Maged1 protein, mouse; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; D025803:Tumor Suppressor Protein p14ARF