The αE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells

Abstract

The acquisition of invasiveness is a crucial step in the malignant progression of cancer. In cancers of the colon and of other organs the E-cadherin/catenin complex, which is implicated in homotypic cell-cell adhesion as well as in signal transduction, serves as a powerful inhibitor of invasion. We show here that one allele of the aE-catenin (CTNNA1) gene is mutated in the human colon cancer cell family HCT-8, which is identical to HCT-15, DLD-1 and HRT-18. Genetic instability, due to mutations in the HMSH6 (also called GTBP) mismatch repair gene, results in the spontaneous occurrence of invasive variants, all carrying either a mutation or exon skipping in the second aE-catenin allele. The aE-catenin gene is therefore, an invasionsuppressor gene in accordance with the two-hit model of Knudsen for tumour-suppressor genes.

Bile acids stimulate invasion and haptotaxis in human colorectal cancer cells through activation of multiple oncogenic signaling pathways

“…All results are statistically significant (P50.05) from the control stimulation measured in the presence of LCA changes in cell-cell and cell-matrix adhesion, and random motility upon treatment with LCA (data not shown). BA stimulate both invasion and haptotaxis in human colon cancer cells HCT-8/E11, possessing a functional E-cadherin/catenin complex, but not in its aE-catenin-deficient derivative HCT-8/E11R1 cell line (Vermeulen et al, 1999). These results indicate that LCA-induced invasion and haptotaxis require functional E-cadherin/catenin complexes, as shown previously for the pro-invasive agents HGF, leptin and trefoil peptides .…”

“…The human colon cancer HCT-8/E11 cell line and its aEcatenin-deficient round subclone HCT-8/E11R1 have been described (Vermeulen et al, 1995(Vermeulen et al, , 1999. Both HCT-8/E11 and HCT-8/E11R1 cell lines were maintained in RPMI-1640 medium (Life Technologies, Ghent, Belgium), supplemented with 10% heat-inactivated fetal bovine serum (FBS), 1 mM sodium pyruvate, 100 mg/ml streptomycin, 250 IU/ml penicillin and 2.5 mg/ml fungizone.…”

A cancer-associated DNA polymerase δ variant modeled in yeast causes a catastrophic increase in genomic instability

“…The proportion of these mutations becomes even higher when the MMR defect of DLD-1 cells is suppressed by exogenous expression of MSH6 (29). The DLD-1 cells are also known to carry homozygous, nonsilent mutations in the APC gene, as well as mutations affecting RAS, p53, and αE-catenin (12,(33)(34)(35). All of them, with the exception of the APC mutations, are GC→AT transitions or GC→TA transversions.…”

Prediction of Tumour Tissue Diffusion Coefficients of Hypoxia-Activated Prodrugs from Physicochemical Parameters

“…The cell lines that provided the fastest and slowest transport were clones with rounded (Ra) or epithelial (Ea) morphology, respectively, which were selected from the parental HCT8 cell line; the latter is hemizygous for the α-E-catenin gene (CTNNA1) and is known to segregate, at high frequency, to round morphology α-E-catenin-null variants lacking adherens junctions. [49] Surprisingly, the HCT-Ra line appears to express normal levels of α-E-catenin, [47] but it nonetheless fails to form tight intercellular junctions. Across the four cell lines there appeared to be an inverse correlation between urea flux and cellular packing density observed by microscopy ( Fig.…”