A central role for cadherin signaling in cancer

Antonis Kourtidis, Ruifeng Lu, Lindy J. Pence, Panagiotis Z Anastasiadis

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Cadherins are homophilic adhesion molecules with important functions in cell-cell adhesion, tissue morphogenesis, and cancer. In epithelial cells, E-cadherin accumulates at areas of cell-cell contact, coalesces into macromolecular complexes to form the adherens junctions (AJs), and associates via accessory partners with a subcortical ring of actin to form the apical zonula adherens (ZA). As a master regulator of the epithelial phenotype, E-cadherin is essential for the overall maintenance and homeostasis of polarized epithelial monolayers. Its expression is regulated by a host of genetic and epigenetic mechanisms related to cancer, and its function is modulated by mechanical forces at the junctions, by direct binding and phosphorylation of accessory proteins collectively termed catenins, by endocytosis, recycling and degradation, as well as, by multiple signaling pathways and developmental processes, like the epithelial to mesenchymal transition (EMT). Nuclear signaling mediated by the cadherin associated proteins β-catenin and p120 promotes growth, migration and pluripotency. Receptor tyrosine kinase, PI3K/AKT, Rho GTPase, and HIPPO signaling, are all regulated by E-cadherin mediated cell-cell adhesion. Finally, the recruitment of the microprocessor complex to the ZA by PLEKHA7, and the subsequent regulation of a small subset of miRNAs provide an additional mechanism by which the state of epithelial cell-cell adhesion affects translation of target genes to maintain the homeostasis of polarized epithelial monolayers. Collectively, the data indicate that loss of E-cadherin function, especially at the ZA, is a common and crucial step in cancer progression.

Original languageEnglish (US)
JournalExperimental Cell Research
DOIs
StateAccepted/In press - Feb 13 2017

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Keywords

  • Cancer progression
  • Cell-cell adhesion
  • E-cadherin
  • EMT
  • Kaiso
  • MiRNA
  • P120 catenin
  • PLEKHA7
  • Rho GTPases
  • β-catenin

ASJC Scopus subject areas

  • Cell Biology

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