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

Authors
 Minjeong Jang  ;  Ilkyoo Koh  ;  Jae Eun Lee  ;  Ju Yeon Lim  ;  Jae-Ho Cheong  ;  Pilnam Kim 
Citation
 BIOMATERIALS SCIENCE, Vol.6(10) : 2704-2713, 2018 
Journal Title
BIOMATERIALS SCIENCE
ISSN
 2047-4830 
Issue Date
2018
MeSH
Antigens, CD ; Antimetabolites, Antineoplastic/pharmacology ; Cadherins/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Extracellular Matrix/metabolism* ; Fluorouracil/pharmacology ; Focal Adhesion Kinase 1/antagonists & inhibitors ; Focal Adhesion Kinase 1/metabolism ; Humans ; Integrin beta Chains/metabolism ; Stomach Neoplasms/metabolism* ; Tumor Microenvironment ; beta Catenin/metabolism*
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 differentially regulates cancer cell phenotype and may have significant implications for the design of biomaterials with appropriate physical properties for in vitro tumor models.
Full Text
https://pubs.rsc.org/en/Content/ArticleLanding/2018/BM/C8BM00843D#!divAbstract
DOI
10.1039/c8bm00843d
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167169
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