Transcriptional regulation of cadherins during development and carcinogenesis.
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.
Peinado
Héctor
H
Department of Biochemistry, Faculty of Medicine, Universidad Autónoma de Madrid, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid. Spain.
Portillo
Francisco
F
Cano
Amparo
A
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002118:Calcium; D018450:Disease Progression; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D009361:Neoplasm Invasiveness; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic
D015820:Cadherins; D002118:Calcium