Multiple pathways regulate Cten in colorectal cancer without a Tensin switch.
Int J Exp Pathol
; 96(6): 362-9, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26852686
ABSTRACT
CTEN/TNS4 is a member of the Tensin gene family. It localizes to focal adhesions and induces cell motility. The mechanisms regulating Cten expression are unclear although we have shown regulation by Kras in the colon and pancreas. In normal mammary cell lines, it is reportedly upregulated by epidermal growth factor receptor (EGFR) and STAT3 signalling and upregulation is accompanied by downregulation of Tensin 3 (Tensin switch). In this study, we investigated the roles of EGFR and STAT3 signalling in the regulation of Cten in colorectal cancer (CRC). In addition, we investigated calpain--a regulator of focal adhesion-associated proteins whose relevance to Cten has not been investigated. CRC cell lines were stimulated with epidermal growth factor (EGF). This resulted in an increase in Cten and Tensin 3 protein. Kras was knocked down and this resulted in downregulation of Cten and Tensin 3. We next investigated the role of STAT3 signalling. Activation and knockdown of STAT3 resulted in downregulation and upregulation, respectively, of Cten. Inhibition of calpain resulted in upregulation of both Cten and Tensin 3. As the regulators of Cten also seemed to regulate Tensin 3, we tested the interaction between Cten and Tensin 3. Cten was forcibly expressed or knocked down resulting, respectively, in upregulation and downregulation of Tensin 3. We conclude that in CRC, Cten is upregulated by EGFR and Kras but downregulated by STAT3. We show that calpain may be a negative regulator of Cten and that a Tensin switch does not occur and, if anything, Cten stabilizes Tensin 3.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Proteínas dos Microfilamentos
Limite:
Humans
Idioma:
En
Revista:
Int J Exp Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido