Open AccessE‐cadherin expression increases cell proliferation by regulating energy metabolism through nuclear factor‐κB in AGS cells
Author(s) -
Park Song Yi,
Shin JeeHye,
Kee SunHo
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13321
Subject(s) - wnt signaling pathway , cadherin , microbiology and biotechnology , cell growth , signal transduction , cell adhesion , cell culture , beta catenin , biology , catenin , cancer cell , cell , chemistry , cancer research , cancer , biochemistry , genetics
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, EC 96, from AGS cells that featured undetectable E‐cadherin expression and a high level of Wnt signaling. In EC 96 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, EC 96 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.