Transcriptional regulation of cadherins during development and carcinogenesis.

By H. Peinado, F. Portillo, A. Cano. International Journal of Developmental Biology, 2004

612 citations recorded by the source corpus.

The cadherin superfamily of Ca(2+)-dependent homophilic adhesion molecules plays a critical role in regulating cell-to-cell interactions. During development, the expression of different cadherins is highly dynamic, since they are associated with the morphogenesis, establishment and/or maintenance of different tissues. Alterations in cadherin expression or function occur frequently during carcinogenesis, such as the loss of the epithelial cadherin (E-cadherin) and/or the aberrant expression of other cadherins. Indeed, the aberrant expression of cadherins has been detected during carcinoma invasion, a process which is reminiscent of the epithelial-mesenchymal transition (EMT) so important in many critical developmental processes. The functional regulation of cadherins can occur at many different levels, from transcriptional regulation to the control of the strength of the cadherin-mediated cell-cell interaction. In this review, we will focus on the transcriptional control of cadherin expression, both in development and carcinogenesis, paying particular attention to the regulation of E-cadherin given its proposed role as a suppressor of invasion. We will discuss the main genetic and epigenetic mechanisms involved in down-regulating E-cadherin expression, and we will analyse the mechanisms involved in regulating EMT, in an attempt to elucidate which elements are common to this process in both physiological and pathological situations.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/9f01fada1bcdfe5889af778084ff17fdaea62003

How researchers see this paper

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In Molecular Biology

1. M. Nieto
2. A. Cano
3. J. P. Thiery
4. Thomas Brabletz
5. R. Weinberg
6. E. Hay
7. H. Peinado
8. D. Medici

In Oncology

1. M. Nieto
2. Thomas Brabletz
3. R. Weinberg
4. A. Cano
5. J. P. Thiery
6. E. Hay
7. D. Medici
8. David M. Gonzalez

Citations in the corpus

• E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer (2009, neutral): “cancer cells [186].”
• The transcription factor ZEB1 (δEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity (2007, background): “Yet, numerous studies have shown a negative impact of Snail1 on E-cadherin expression and epithelial differentiation (Batlle et al., 2000; Cano et al., 2000; Palmer et al., 2004; Peinado et al. 2004; Pena et al., 2005, 2006).”
• Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. (2009, background): “Among the high number of factors and mechanisms specifically implicated in E-cadherin regulation repressors of gene expression have strongly been associated with EMT and tumour progression [73–75].”
• The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it (2005, background): “19A,B) in the E-cadherin promoter to totally repress the E-cadherin gene (Peinado et al., 2004).”
• Cadherin switching (2008, background): “Each of these mechanisms has been implicated in various tumor types (reviewed in Peinado et al., 2007; Peinado et al., 2004).”
• Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. (2008, positive): “Unsupervised hierarchical clustering of the tumors and statistical analysis showed that up-regulation of EMTmarkers (vimentin, smoothmuscle-actin, N-cadherin, and cadherin-11) and overexpression of proteins involved in extracellular matrix remodeling and invasion (SPARC, laminin, and fascin), togeth”
• Complex networks orchestrate epithelial–mesenchymal transitions (2006, background): “For example, mesenchymal cells do not express epithelial (E)-cadherin, whereas epithelial cells d”
• Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression (2010, background): “Additional cell-cell junctions including adherens and gap junctions begin to disassemble and the underlying basement membrane is degraded [20].”
• Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? (2007, background): “The modification of chromatin structure has emerged as a major regulatory event promoted by these proteins during EM”
• The ins and outs of the epithelial to mesenchymal transition in health and disease. (2011, background): “Snail-mediated cadherin repression and EMT is assisted by the recruitment of SIN3A, histone deacetylases, and components of the Polycomb 2 complex (Herranz et al. 2008, Peinado et al. 2004a).”
• Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? (2005, background): “Evidence of EMT in clinical cancer specimens include loss or delocalization of junctional E-cadherin (21), switch to other cadherins (e.g., N-cadherin replaces E-cadherin in prostate cancer; ref.”
• Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. (2005, background): “The expression of Zeb-1 was recently shown to correlate with the degree of EMT in breast cancer cells (28), and E-cadherin has been shown to be highly regulated and repressed at the transcriptional level by factors including Snail, Slug, Twist, and ZEB (29, 30), likely requiring the recruitment of C”
• The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 (2008, background): “ZEB1 and SIP1 are able to initiate EMT by binding to E-boxes within the E-cadherin promoter and repressing its transcriptio”
• The role of epithelial-mesenchymal transition in cancer pathology. (2007, background): “Among these, invasive lobular carcinoma of the breast and diffuse gastric carcinoma are known to harbour inactivating mutations of the E-cadherin gene in about 50% of cases.(1,12,15,23) The Ecadherin dependent reduction of cell-cell adhesion in these tumours underlies the extensive permeation of car”
• Signaling mechanisms of the epithelial-mesenchymal transition (2014, background): “Additionally, Twist1 is responsible for the expression of several microRNAs (miRNAs), which mediate inhibition of HOXD1 expression and its downstream target genes (43).”
• Transcriptional regulation of cell polarity in EMT and cancer (2008, background): “One of the earliest steps in EMT is the loss of E-cadherin function, and in fact it is generally accepted that EMT-inducing factors initiate epithelial reorganization by impairing the expression or function of E-cadherin (Peinado et al., 2004; Jeanes et al., 2008).”