Expression of µ-protocadherin is negatively regulated by the activation of the ß-catenin signaling pathway in normal and cancer colorectal enterocytes.
Cell Death Dis
; 7: e2263, 2016 06 16.
Article
em En
| MEDLINE
| ID: mdl-27310872
ABSTRACT
Mu-protocadherin (MUCDHL) is an adhesion molecule predominantly expressed by colorectal epithelial cells which is markedly downregulated upon malignant transformation. Notably, treatment of colorectal cancer (CRC) cells with mesalazine lead to increased expression of MUCDHL, and is associated with sequestration of ß-catenin on the plasma membrane and inhibition of its transcriptional activity. To better characterize the causal relationship between ß-catenin and MUCDHL expression, we performed various experiments in which CRC cell lines and normal colonic organoids were subjected to culture conditions inhibiting (FH535 treatment, transcription factor 7-like 2 siRNA inactivation, Wnt withdrawal) or stimulating (LiCl treatment) ß-catenin activity. We show here that expression of MUCDHL is negatively regulated by functional activation of the ß-catenin signaling pathway. This finding was observed in cell culture systems representing conditions of physiological stimulation and upon constitutive activation of ß-catenin in CRC. The ability of MUCDHL to sequester and inhibit ß-catenin appears to provide a positive feedback enforcing the effect of ß-catenin inhibitors rather than serving as the primary mechanism responsible for ß-catenin inhibition. Moreover, MUCDHL might have a role as biomarker in the development of CRC chemoprevention drugs endowed with ß-catenin inhibitory activity.
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Base de dados:
MEDLINE
Assunto principal:
Caderinas
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Regulação Neoplásica da Expressão Gênica
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Neoplasias do Colo
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Enterócitos
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Beta Catenina
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article