C-terminal Tensin-like (CTEN) is an oncogene which alters cell motility possibly through repression of E-cadherin in colorectal cancer.
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.
Albasri
Abdulkader
A
Division of Pathology, Nottingham University, Nottingham NG7 2UH, UK.
Seth
Rashmi
R
Jackson
Darryl
D
Benhasouna
Ahmed
A
Crook
Simon
S
Nateri
Abdolrahman S
AS
Chapman
Roger
R
Ilyas
Mohammad
M
D015820:Cadherins / Q000235:genetics*; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000235:genetics*; D018613:Microscopy, Confocal; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019311:Staurosporine / Q000627:therapeutic use; D000070876:Tensins; D014162:Transfection
D015820:Cadherins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D000070876:Tensins; D019311:Staurosporine