Regulation of the Invasion Suppressor Function of the Cadherin/Catenin Complex

Vermeulen, Stefan; Marck, Veerle Van; Hoorde, Leen Van; Roy, Frans van; Bracke, Marc; Mareel, Marcus

doi:10.1016/s0344-0338(96)80091-4

Cited by 44 publications

(30 citation statements)

References 75 publications

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“…In some colon cancer cell lines, de®ciencies at the mRNA and protein level were described for E-cadherin and aE-catenin but not for b-catenin (Vermeulen et al, 1996). Cultivating the human colon cancer cell line HCT-8, we found that invasive variants regularly emerged from noninvasive clones (Vermeulen et al, 1995a).…”

Section: Introductionmentioning

confidence: 75%

“…To our knowledge, there are no other examples of regular mutational downmodulation of aE-catenin in short-term experimental systems. De®ciencies in aEcatenin, associated with loss of function of the Ecadherin/catenin complex, were found in other human cancer cell lines from prostate (PC-3; PPC-1; ALVA-31) (Bussemakers et al, 1996), lung (PC-9), and colon (Clone A; MIP 101; CCL222) (Vermeulen et al, 1996). Their derivation from aE-catenin-positive parental cells was, however, not investigated.…”

Section: Hct-8 Is a Genetically Unstable Cell Linementioning

confidence: 99%

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

Vermeulen

Nollet

Teugels³

et al. 1999

Oncogene

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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.

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Section: Introductionmentioning

confidence: 75%

Section: Hct-8 Is a Genetically Unstable Cell Linementioning

confidence: 99%

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

Vermeulen

Nollet

Teugels³

et al. 1999

Oncogene

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“…12 Suggestively originating from the reserve cells, SILs are believed to inherit some differentiation features of their progenitors. SILs express mostly cytokeratins 6,8,17, and 18; in this they resemble reserve cell phenotype/differentiation, although they also express some keratins (5,14,19) common to both the reserve cells and the basal cells of normal squamous epithelium. 14 In this study, we have analyzed immunohistochemically whether the intercellular adhesions typical for the reserve and basal cells are reproduced in SILs cells during the development and progression of these lesions.…”

mentioning

confidence: 93%

“…2,5,6 Disturbances in cell differentiation in epithelia observed during carcinogenesis correlate clearly with changes in intercellular adhesion. 7,8 E-cadherin, being in the center of cellcell interactions, is usually affected during tumor progression and invasion in many types of epithelial tumors. 4,7 Affected E-cadherin-mediated adherens junctions result in changes in cell phenotype, increased cell invasiveness, increased cell motility, and other changes in vital cell functions.…”

mentioning

confidence: 99%

Changing Roles of Cadherins and Catenins during Progression of Squamous Intraepithelial Lesions in the Uterine Cervix

Boer

Dorst²,

Krieken

et al. 1999

The American Journal of Pathology

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Uterine cervix represents a convenient model for the study of the gradual transformation of normal squamous epithelium via low-to high-grade squamous intraepithelial lesions (SILs). Because SIL , on the basis of the cytokeratins expressed , are thought to originate from the reserve cells , we analyzed whether SILs also show a reserve cell phenotype with respect to intercellular interactions. The changes in expression and subcellular localization of the components of the adherens junction and desmosomal complexes were investigated in normal , metaplastic , and premalignant cervical epithelium , as well as in cell cultures derived from these tissues. The results suggest that 1) during progression of SILs , E-cadherin is suppressed, with its role in cell-cell connections diminishing; 2) P-cadherin , in contrast , becomes the predominant cadherin in high-grade SILs; 3) the level of cellular ␣-catenin is dramatically decreased in high-grade SILs; 4) the level of ␤-catenin is decreased during progression of SILs , with plakoglobin suggestively becoming the predominant catenin mediating connection of cadherins to the cytoskeleton; 5) the assembly of desmosomes is affected during progression of SILs and is accompanied by a dramatically decreased expression for desmogleins and desmoplakins (I , II); and 6) expression of differentiation markers (involucrin , CK13) in high-grade SILs seems to be controlled by P-cadherin as opposed to E-cadherin in the normal tissue counterpart. We conclude that during development of cervical lesions substantial (

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“…Localized at the cell membrane protein Cadherin, it effects cell adhesion by arranging the binding of ␣-catenin to cytosolic filaments (1)(2)(3). The continuous Cadherin-bound distribution of ␤-catenin is a characteristic of regular epithelia with intact cell adhesion (4,5).…”

mentioning

confidence: 99%

β-Catenin in Soft tissue Sarcomas: Expression is Related to Proliferative Activity in High-Grade Sarcomas

et al. 2000

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Besides its role in cell adhesion, ␤-catenin exerts a function as an oncoprotein. The aim of this study was the characterization of its expression, possible mutation, and the assessment of ␤-catenin as a prognostic indicator for soft tissue sarcomas. A total of 115 soft tissue sarcomas were analyzed using immunohistochemistry, immunogold-electron microscopy, and DNA analysis. Information from 56 patients was available for follow-up. A statistically significant correlation was found between intracellular distribution of ␤-catenin and the proliferative activity (MIB-1 expression) in high-grade sarcomas (P ‫؍‬ .0008). ␤-catenin was identified with intracytoplasmic and nuclear accumulation, showing additional membranous staining in sarcomas with epithelioid pattern. Ultrastructurally, a colocalization between ␤-catenin and nuclear heterochromatin was demonstrated. In 22 analyzed tumors, only one (yet undescribed) mutation of the ␤-catenin gene (C-A transversion) could be detected. Prognostic validity of the cellular expression of ␤-catenin, however, was not proven. Apart from its membranous function as an effective molecule for cell-adhesion in sarcomas with epithelioid pattern, ␤-catenin may act as an oncoprotein in sarcomas with intracytoplasmic and nuclear localization with binding to nuclear DNA. A previously discussed stimulation of cell proliferation caused by an increased ␤-catenin level can also be postulated for high-grade soft tissue sarcomas in correlation with the rate of proliferation. Mutations of the ␤-catenin gene are probably of lesser importance for the accumulation of ␤-catenin in soft tissue sarcomas.

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Regulation of the Invasion Suppressor Function of the Cadherin/Catenin Complex

Cited by 44 publications

References 75 publications

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

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

Changing Roles of Cadherins and Catenins during Progression of Squamous Intraepithelial Lesions in the Uterine Cervix

β-Catenin in Soft tissue Sarcomas: Expression is Related to Proliferative Activity in High-Grade Sarcomas

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