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Title: A central role for cadherin signaling in cancer

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 adhesionmore » 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. - Highlights: • General review of the cadherin-catenin complex. • Nuclear signaling events regulated by β-catenin, p120, and E-cadherin. • Cadherin dysfunction in cancer. • Crosstalk between cadherin complexes and the RNAi machinery.« less

Authors:
 [1]; ;  [2];  [2]
  1. Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425 (United States)
  2. Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224 (United States)
Publication Date:
OSTI Identifier:
22738150
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 358; Journal Issue: 1; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADHESION; COMPLEXES; NEOPLASMS; SIGNALS

Citation Formats

Kourtidis, Antonis, Lu, Ruifeng, Pence, Lindy J., and Anastasiadis, Panos Z., E-mail: panos@mayo.edu. A central role for cadherin signaling in cancer. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.04.006.
Kourtidis, Antonis, Lu, Ruifeng, Pence, Lindy J., & Anastasiadis, Panos Z., E-mail: panos@mayo.edu. A central role for cadherin signaling in cancer. United States. doi:10.1016/J.YEXCR.2017.04.006.
Kourtidis, Antonis, Lu, Ruifeng, Pence, Lindy J., and Anastasiadis, Panos Z., E-mail: panos@mayo.edu. Fri . "A central role for cadherin signaling in cancer". United States. doi:10.1016/J.YEXCR.2017.04.006.
@article{osti_22738150,
title = {A central role for cadherin signaling in cancer},
author = {Kourtidis, Antonis and Lu, Ruifeng and Pence, Lindy J. and Anastasiadis, Panos Z., E-mail: panos@mayo.edu},
abstractNote = {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. - Highlights: • General review of the cadherin-catenin complex. • Nuclear signaling events regulated by β-catenin, p120, and E-cadherin. • Cadherin dysfunction in cancer. • Crosstalk between cadherin complexes and the RNAi machinery.},
doi = {10.1016/J.YEXCR.2017.04.006},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 1,
volume = 358,
place = {United States},
year = {2017},
month = {9}
}