E-cadherin expression increases cell proliferation by regulating energy metabolism through nuclear factor-κB in AGS cells

Song Yi Park, Jee Hye Shin, Sun Ho Kee

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


β-Catenin is a central player in Wnt signaling, and activation of Wnt signaling is associated with cancer development. E-cadherin in complex with β-catenin mediates cell–cell adhesion, which suppresses β-catenin-dependent Wnt signaling. Recently, a tumor-suppressive role for E-cadherin has been reconsidered, as re-expression of E-cadherin was reported to enhance the metastatic potential of malignant tumors. To explore the role of E-cadherin, we established an E-cadherin-expressing cell line, EC96, from AGS cells that featured undetectable E-cadherin expression and a high level of Wnt signaling. In EC96 cells, E-cadherin re-expression enhanced cell proliferation, although Wnt signaling activity was reduced. Subsequent analysis revealed that nuclear factor-κB (NF-κB) activation and consequent c-myc expression might be involved in E-cadherin expression-mediated cell proliferation. To facilitate rapid proliferation, EC96 cells enhance glucose uptake and produce ATP using both mitochondria oxidative phosphorylation and glycolysis, whereas AGS cells use these mechanisms less efficiently. These events appeared to be mediated by NF-κB activation. Therefore, E-cadherin re-expression and subsequent induction of NF-κB signaling likely enhance energy production and cell proliferation.

Original languageEnglish
Pages (from-to)1769-1777
Number of pages9
JournalCancer Science
Issue number9
Publication statusPublished - 2017 Sept

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2015R1D1A1A09056775).

Funding Information:
National Research Foundation of Korea, (Grant/Award Number: ‘NRF-2015R1D1A1A09056775′)

Publisher Copyright:
© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.


  • Axin
  • E-cadherin
  • NF-κB
  • mitochondria metabolism
  • β-Catenin mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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