title: 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.
authors.affiliation: Division of Pathology, Nottingham University, Nottingham NG7 2UH, UK.
authors.forename: Abdulkader
authors.initials: A
authors.lastname: Albasri
authors.forename: Rashmi
authors.initials: R
authors.lastname: Seth
authors.forename: Darryl
authors.initials: D
authors.lastname: Jackson
authors.forename: Ahmed
authors.initials: A
authors.lastname: Benhasouna
authors.forename: Simon
authors.initials: S
authors.lastname: Crook
authors.forename: Abdolrahman S
authors.initials: AS
authors.lastname: Nateri
authors.forename: Roger
authors.initials: R
authors.lastname: Chapman
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ilyas
mesh_terms: 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
chemical_list: D015820:Cadherins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D000070876:Tensins; D019311:Staurosporine