TCF12 protein functions as transcriptional repressor of E-cadherin, and its overexpression is correlated with metastasis of colorectal cancer.
J Biol Chem
; 287(4): 2798-809, 2012 Jan 20.
Article
em En
| MEDLINE
| ID: mdl-22130667
ABSTRACT
A correlation of TCF12 mRNA overexpression with colorectal cancer (CRC) metastasis was suggested by microarray data and validated by the survey of 120 patients. Thirty-three (27.5%) of the 120 patients showed tumor TCF12 mRNA overexpression and had a higher rate of metastatic occurrence (p = 0.020) and a poorer survival outcome (p = 0.014). Abundant TCF12 levels were also observed in human CRC cell lines such as SW620 and LoVo, but a relatively low level was detected in SW480 cells. Knockdown of TCF12 expression in SW620 and LoVo cells drastically reduced their activities of migration, invasion, and metastasis. Tight cell-cell contact and an increase in E-cadherin but a concomitant decrease in fibronectin were observed in TCF12-knockdown cells. Connexin 26, connexin 43, and gap-junction activity were also increased upon TCF12-knockdown. In contrast, ectopic TCF12 overexpression in SW480 cells facilitated fibronectin expression and cell migration and invasion activities but diminished cellular levels of E-cadherin, connexin 26, connexin 43, and gap junction. A physical association of TCF12 with the E-cadherin promoter was evidenced by chromatin immunoprecipitation assay. TCF12 was tightly correlated with cellular expression of Bmi1 and EZH2 and was co-immunoprecipitable with Bmi1 and EZH2, suggesting that TCF12 transcriptionally suppressed E-cadherin expression via polycomb group-repressive complexes. Clinically, TCF12 mRNA overexpression was also correlated with E-cadherin mRNA down-regulation in the tumor tissues of our 120 patients (p = 0.013). These studies suggested that TCF12 functioned as a transcriptional repressor of E-cadherin and its overexpression was significantly correlated with the occurrence of CRC metastasis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Neoplasias Colorretais
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Caderinas
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Regulação Neoplásica da Expressão Gênica
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Proteínas de Neoplasias
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Taiwan