E-cadherin—catenin cell—cell adhesion complex and human cancer

Abstract

Background: The E-cadherin±catenin complex plays a crucial role in epithelial cell±cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. Recently, much progress has been made in understanding the interaction between the different components of this protein complex and how this cell±cell adhesion complex is modulated in cancer cells.Methods: This is an update of the role of the E-cadherin±catenin complex in human cancers. It emphasizes new features and the possible role of the complex in clinical practice, discussed in the light of 165 references obtained from the Medline database from 1995 to 1999.Results: More evidence is now appearing to suggest that disturbance in protein±protein interaction in the E-cadherin±catenin adhesion complex is one of the main events in the early and late steps of cancer development. An inverse correlation is found between expression of the E-cadherin±catenin complex and the invasive behaviour of tumour cells. Therefore, E-cadherin±catenin may become a signi®cant prognostic marker for tumour behaviour. Besides its role in establishing tight cell±cell adhesion, bcatenin plays a major role in cell signalling and promotion of neoplastic growth. This suggests its dual role as a tumour suppressor and as an oncogene in human cancers. Conclusion: Recent developments show that the E-cadherin±catenin complex is more than a`sticky molecular complex'. Further studies may yield greater insight into the early molecular interactions critical to the initiation and progression of tumours. This should aid the development of novel strategies for both prevention and treatment of cancer.

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

“…Even though the correlation between a reorganisation of E-cadherin/b-catenin complexes and MCP-1 expression has never been reported before, the large amount of data from the literature, associating E-cadherin/b-catenin complexes reorganization and the expression of an invasive phenotype 20,22,[40][41][42][43][44] strengthen our findings. Furthermore, our data are in agreement with data reporting MCP-1 expression in a variety of human tumour cell lines including gastric, 10 ovarian, 45 breast, 9 melanoma, 46 pancreatic 7 and neuroblastoma cancer cell lines.…”

“…In pathological processes including cancer progression, bcatenin can accumulate in the cytoplasm and then translocate to the nucleus where it binds transcription factors of the TCF/LEF family (T Cell Factor/Lympho€ ıd Enhanced Factor), leading to the activation of specific genes. [21][22][23] The accumulation of cytoplasmic b-catenin and its translocation to the nucleus has been associated with epithelial cell migration and invasion in various physiological and pathological processes including tumour progression. 21,[23][24][25][26] Several b-catenin/TCF target genes have now been identified.…”

The intercellular adhesion molecule, cadherin-10, is a marker for human prostate luminal epithelial cells that is not expressed in prostate cancer

“…8,9 The role of cadherins, particularly the prototypical classical cadherin, epithelial (E)-cadherin, has been studied in detail in relation to metastatic potential and prognosis in carcinoma. [10][11][12][13] In general, loss of E-cadherin expression or function is associated with more aggressive tumours and poor prognosis. Expression of E-cadherin is typically reduced in prostate cancer.…”

E-cadherin in canine mast cell tumors: Decreased expression and altered subcellular localization in Grade 3 tumors

“…Several studies involving human and canine neoplasms have demonstrated that the expression of cadherins is altered during tumor progression (Wijnhoven et al, 2000;Menke et al, 2001;Bankfalvi et al, 2002;Gama et al, 2007;Brunetti et al, 2003;De Matos et al, 2007;Polton et al, 2007), and that more aggressive phenotypes express less E-cadherin (Torres et al, 2005;Brunetti et al, 2003;De Matos et al, 2007;Gama et al, 2007). More recent studies have shown that a decrease in E-cadherin expression or its translocation from the plasma membrane to the cytoplasm and/or nucleus can be crucial events in adherent junction destabilization (Gloushankova, 2008;Salahshor et al, 2008;Elston et al, 2009;Knirsh et al, 2009).…”

“…Therefore, events that disrupt the complex cadherin-catenin-cytoskeleton lead to a destabilization of cellcell adhesion and ultimately a reorganization of the actin cytoskeleton (Mareel and Leroy, 2003). It has been hypothesized that alterations in E-cadherin expression might be a crucial event in malignant tumor progression and growth (Wijnhoven et al, 2000;Menke et al, 2001;Bankfalvi et al, 2002;Nowak et al, 2008).…”