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PMID: 21746881 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Molecular and cellular biology ·Vol. 31 ·No. 19 ·2011-10-00 ·Pages 4036-51

Kumar S, Park SH, Cieply B, Schupp J, Killiam E, Zhang F, Rimm DL, Frisch SM

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.

MeSH Terms
Animals Ankyrins/genetics,metabolism Anoikis/physiology Antigens, Neoplasm/genetics,metabolism Cadherins/genetics,metabolism Cell Line, Tumor Epithelial Cells/cytology,physiology Epithelial-Mesenchymal Transition/physiology Humans Mice Neoplasm Proteins/genetics,metabolism RNA, Small Interfering/genetics,metabolism Signal Transduction/physiology T-Box Domain Proteins/genetics,metabolism Tumor Suppressor Protein p14ARF/genetics,metabolism Two-Hybrid System Techniques
Chemicals
ANK3 protein, human Ankyrins Antigens, Neoplasm Cadherins MAGED1 protein, human Maged1 protein, mouse Neoplasm Proteins RNA, Small Interfering T-Box Domain Protein 2 T-Box Domain Proteins Tumor Suppressor Protein p14ARF
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kumar Sanjeev
Department of Biochemistry and Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506, USA.
Park Sun Hee
Cieply Benjamin
Schupp Jane
Killiam Elizabeth
Zhang Fan
Rimm David L
Frisch Steven M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01342-10
Published
2011-10-00
Epub
2011-00-11
Pages
4036-51
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC3187352
Subset
IM
Grants
NCRR NIH HHS · P20 RR16440 · United States
NCI NIH HHS · R01 CA123359 · United States
NCRR NIH HHS · P20 RR016440 · United States
NCI NIH HHS · R01CA123359 · United States
NCRR NIH HHS · S10 RR020866 · United States
NIGMS NIH HHS · P30 GM103488 · United States
NCRR NIH HHS · RR020866 · United States
External Links
PubMed source DOI: 10.1128/MCB.01342-10 PMC Full Text View journal details
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