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Multiple pathways regulate Cten in colorectal cancer without a Tensin switch
Author(s) -
Thorpe Hannah,
Akhlaq Maham,
Jackson Darryl,
Ghamdi Saleh Al,
Storr Sarah,
Martin Stewart,
Ilyas Mohammad
Publication year - 2015
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12154
Subject(s) - tensin , downregulation and upregulation , focal adhesion , cancer research , kras , microbiology and biotechnology , biology , signal transduction , pi3k/akt/mtor pathway , pten , cancer , colorectal cancer , biochemistry , genetics , gene
Summary CTEN / TNS 4 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 STAT 3 signalling and upregulation is accompanied by downregulation of Tensin 3 (Tensin switch). In this study, we investigated the roles of EGFR and STAT 3 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 STAT 3 signalling. Activation and knockdown of STAT 3 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 STAT 3. 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.