C‐terminal Tensin‐like (CTEN) is an oncogene which alters cell motility possibly through repression of E‐cadherin in colorectal cancer

Abstract

The Tensin gene family encodes proteins thought to modulate integrin function. C-terminal Tensin-like (CTEN) is a member of the Tensin gene family which lacks the N-terminus actin-binding domain. Cten is reported to have both oncogenic and tumour-suppressor functions. We investigated the role that Cten may play in colorectal cancer (CRC). By quantitative RT-PCR CTEN is up-regulated (i.e. > two-fold increase) in 62% of cell lines and 69% of tumours compared with normal mucosa, consistent with CTEN being a possible oncogene. Stable transfection of HCT116 and SW480 (CRC cell lines with low endogenous Cten expression) with a Cten expression vector gave identical results in both cell lines. Forced Cten expression did not cause change in cell numbers, although it did confer resistance to staurosporine-induced apoptosis (p < 0.005). Cten also induced epithelial-mesenchymal transition (EMT) in tumour cells accompanied by a significant increase in both cell migration (transwell migration and cell wounding assays, p < 0.001 and p < 0.05, respectively) and cell invasion (invasion through Matrigel, p < 0.001). Given the observed EMT, we investigated the levels of E-cadherin. Cten induction was associated with a reduction in E-cadherin protein expression but not levels of E-cadherin mRNA. These data suggest that CTEN is an oncogene in CRC which stimulates EMT, cell migration and invasion and may therefore have a role in tumour invasion/spread. Furthermore, Cten induction is associated with post-transcriptional repression of E-cadherin.

CTEN (C-terminal tensin-like), a novel oncogene overexpressed in invasive breast carcinoma of poor prognosis

“…Recently, we have reported that CTEN acts as an oncogene in CRC and correlates with changed cell morphology and increased cell motility through repression of E-cadherin protein [6]. In support of this hypothesis, we have found a significant association, in the current study, between CTEN expression and lobular carcinoma that is known to be associated with loss of E-cadherin expression [23].…”

“…For example, we and others have reported, that CTEN acts as an oncogene in colorectal cancer (CRC) and correlates with changed cell morphology and increased cell motility. This is complemented by decreased E-cadherin protein levels, resistance to staurosporine-induced apoptosis and increased colony forming properties [6,7]. In addition, CTEN has been reported to have an oncogenic activity in thymomas, lung and gastric cancers, and in general, its over-expression has been associated with poor prognosis [8][9][10].…”

Cten signals through integrin-linked kinase (ILK) and may promote metastasis in colorectal cancer

“…We have recently shown that high levels of Cten expression are associated with a poor prognosis in breast cancer (Albasri et al, 2011), and similar results have been reported in thymomas, gastric cancers and lung cancers (Sasaki et al, 2003a, b;Sakashita et al, 2008). The impact of Cten expression on clinical outcome may be related to its biological activity, which, in CRC cell lines at least, results in enhanced colony formation, resistance to staurosporineinduced apoptotic stress and increased cell motility (Albasri et al, 2009;Liao et al, 2009). However, the prognostic value of Cten expression in CRCs has hitherto not been reported.…”

“…Although Cten acts as a tumour suppressor in prostate cancer (Lo and Lo, 2002), in many cancers including breast cancer and colorectal cancer (CRC), it acts as an oncogene (Katz et al, 2007;Albasri et al, 2009;Liao et al, 2009). We have recently shown that high levels of Cten expression are associated with a poor prognosis in breast cancer (Albasri et al, 2011), and similar results have been reported in thymomas, gastric cancers and lung cancers (Sasaki et al, 2003a, b;Sakashita et al, 2008).…”

“…Tensin family proteins interact with several structural and signalling molecules such as vinculin, paxillin, Src, focal adhesion kinase, phosphatidylinositol-3-kinase and Crk-associated substrate p130 CAS , actin as well as integrins. As Cten is a recently described gene, data about its downstream targets are sparse, although recent studies suggest that Cten signalling occurs through the Stat3 pathway (Barbieri et al, 2010).Although Cten acts as a tumour suppressor in prostate cancer (Lo and Lo, 2002), in many cancers including breast cancer and colorectal cancer (CRC), it acts as an oncogene (Katz et al, 2007;Albasri et al, 2009;Liao et al, 2009). We have recently shown that high levels of Cten expression are associated with a poor prognosis in breast cancer (Albasri et al, 2011), and similar results have been reported in thymomas, gastric cancers and lung cancers (Sasaki et al, 2003a, b;Sakashita et al, 2008).…”