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Differential Impacts on Tensional Homeostasis of Gastric Cancer Cells Due to Distinct Domain Variants of E-Cadherin

Han Xu1, Katie A Bunde1, Joana Figueiredo2,3

  • 1Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.

Cancers
|June 10, 2022
PubMed

Insights

E-cadherin mutations impact gastric cancer cell tensional homeostasis, with juxtamembrane and intracellular domains being key. Extracellular matrix proteins like Fibronectin and Vitronectin may influence this cellular tension regulation.

Area of Science:

  • Cell Biology
  • Biophysics
  • Cancer Research

Background:

  • Epithelial tissue integrity relies on tensional homeostasis, which is disrupted by E-cadherin dysfunction.
  • E-cadherin mutations are linked to gastric cancer progression and altered tissue function.

Purpose of the Study:

  • To investigate how E-cadherin mutations in different domains affect gastric cancer cell tensional homeostasis.
  • To explore the role of extracellular matrix (ECM) proteins in modulating E-cadherin-mediated cellular tension.

Main Methods:

  • Micropattern traction microscopy was used to measure cellular traction forces in AGS gastric cancer cells.
  • Cells were transfected with wild-type E-cadherin or variants affecting its extracellular, juxtamembrane, or intracellular domains.
  • Cells were cultured on hydrogels functionalized with specific ECM proteins (Fibronectin/Vitronectin or Collagen VI).

Main Results:

  • Mutations in distinct E-cadherin domains differentially affected cellular tensional homeostasis.
  • The juxtamembrane and intracellular domains of E-cadherin were identified as critical for maintaining tensional homeostasis.
  • Fibronectin and Vitronectin promoted adhesive ability in E-cadherin dysfunctional cells, potentially modulating their tensional homeostasis.

Conclusions:

  • E-cadherin's juxtamembrane and intracellular regions are crucial for regulating gastric cancer cell tensional homeostasis.
  • Specific ECM compositions, such as Fibronectin and Vitronectin, can influence cancer cell behavior regarding tensional homeostasis.
  • Understanding these mechanisms could offer new therapeutic targets for gastric cancer.
Keywords:
E-cadherin mutationsextracellular matrix proteinsgastric cancer cellstensional homeostasistraction microscopy

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