Increased extracellular matrix density disrupts E-cadherin/β-catenin complex in gastric cancer cells

Biomaterials Science
Minjeong JangPilnam Kim

Abstract

During gastric cancer (GC) progression, increased extracellular matrix (ECM) deposition, notably collagen type I, correlates with an overall increase in expression of the mesenchymal phenotype. In GC tissue, the intestinal epithelium exhibits impaired cell-cell adhesion and enhanced cell-ECM adhesion. The alteration of intercellular integrity is one of tumorigenesis feature including tumor invasion and metastasis. Using a density-varying ECM, we studied the effect of ECM density on both intercellular- and ECM-interactions according to alterations of ECM-mediated signaling. A dense collagen matrix increases integrin-mediated cell-ECM interactions with phosphorylated FAK and ERK signaling in human gastric adenocarcinoma cells (AGS, MKN74), which regulates GC proliferation and the chemotherapeutic response. In addition, GC cells exhibited a disrupted membranous E-cadherin/β-catenin complex and, remarkably, showed cytoplasmic or nucleic localization of β-catenin in response to collagen density. Furthermore, we found that membranous E-cadherin/β-catenin complex could be recovered by inhibiting the phosphorylation of FAK, which in turn influences the chemotherapeutic effect. These results provide insight into how matrix density diffe...Continue Reading

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Citations

Feb 13, 2020·Cells·Ana Margarida MoreiraJoana Figueiredo
Sep 16, 2019·Journal of Translational Medicine·Shuaishuai XuLiang Liu
Aug 2, 2019·World Journal of Clinical Cases·Mu-Ni HuHuan Deng
Apr 3, 2019·International Journal of Molecular Sciences·Jinglin ZhangWei Kang
May 25, 2020·Cancer Metastasis Reviews·Ana C Martins CavacoLuís Costa
Aug 14, 2019·Tissue Engineering. Part C, Methods·Amir Monemian EsfahaniRuiguo Yang
Aug 3, 2019·International Journal of Molecular Sciences·Sabino RussiVitalba Ruggieri
Jan 14, 2021·International Journal of Molecular Sciences·Hana LeeSeok-Jun Kim
Mar 17, 2021·ACS Biomaterials Science & Engineering·Hyun Jin LeePilnam Kim
Apr 9, 2021·Journal of Biomedical Science·Yu-Chen S H YangKuan Wang
May 29, 2021·Frontiers in Oncology·Yuyi LiXinliang Lu
Aug 24, 2021·Frontiers in Molecular Biosciences·Huichen ZhaoXiao-Bing Chen

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Methods Mentioned

BETA
scanning electron microscopy
confocal microscopy
PCR

Software Mentioned

COMSOL
PrimerBank
COMSOL Multiphysics

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