E-Cadherin and α-Catenin Expression during Tumor Progression of Cervical Carcinoma

Carico, Elisabetta; Atlante, M; Bucci, Barbara; Nofroni, Italo; Vecchione, Andrea

doi:10.1006/gyno.2000.6035

Cited by 47 publications

(56 citation statements)

References 27 publications

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“…E-cadherin is a major adhesion component of epithelial cells, which plays an important role as an invasion suppressor gene. Decrease or loss of E-cadherin expression is a common feature of many human epithelial cancers, including cervical cancer, although a decreased expression of this molecule has been described in metastasis, but not primary tumors (42). Promoter hypermethylation has been proposed as an explanation for the decrease of E-cadherin expression (24,43) and was even suggested as a potential marker for identifying cervical cancer patients at high risk for relapse (32).…”

Section: Discussionmentioning

confidence: 99%

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

Attaleb¹,

W²,

Khyatti³

et al. 2009

oncol res

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Aberrant methylation of tumor suppressor gene promoters has been extensively investigated in cervical cancer. Transcriptional silencing, as a main consequence of hypermethylation of CpG islands, is the predominant mechanism of p16 INK4a and E-cadherin gene inactivation in malignant epithelial tumors. This study was conducted to evaluate the promoter methylation status of p16 INK4a and E-cadherin genes in 22 specimens of cervical carcinomas, four cervical cancer cell lines (HeLa, SiHa, Caski, C33A), and 20 human papillomavirus negative specimens, obtained from normal cervical swabs, using the methylation-specific PCR approach. Hypermethylation of the 5′ CpG island of the p16 INK4a and E-cadherin genes were found in 13 (59.1%) and 10 (45.5%) of 22 cervical cancer samples, respectively. Furthermore, our findings did not show any correlation between promoter methylation of p16 INK4a and E-cadherin genes and clinicopathological parameters, including HPV infection, phenotypic distribution, and stage of the disease. However, hypermethylation of E-cadherin gene promoter appears to be age related in cervical cancer, whereas the frequency of aberrant methylation of p16 INK4a gene promoter is unchanged according to the age of patients. Thus, caution must be made to use these markers in the diagnosis of cervical cancer. However, dietary or pharmaceutical agents that can inhibit these epigenetic events may prevent or delay the development of cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

Attaleb¹,

W²,

Khyatti³

et al. 2009

oncol res

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“…How normal cells lose their ability to form strong adhesions within a tissue is not well understood (2,3). The loss of adhesion between adjoining epithelial cells and the ensuing onset of metastasis occur through an epithelial-to-mesenchymal transition that often correlates with the loss of cytoplasmic protein ␣-catenin and a poor prognosis in a wide range of cancers, including breast (4), esophageal (5), gastric (6,7), cervical (8), and colorectal cancer (9). In normal epithelial tissues, ␣-catenin localizes to junctions that organize at the interface between adjacent epithelial cells through clustering of cell surface adhesion transmembrane molecule cadherin and its association to the cytoskeleton (10,11).…”

mentioning

confidence: 99%

Loss of α-Catenin Decreases the Strength of Single E-cadherin Bonds between Human Cancer Cells

Bajpai

Feng

Krishnamurthy

et al. 2009

Journal of Biological Chemistry

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The progression of several human cancers correlates with the loss of cytoplasmic protein ␣-catenin from E-cadherin-rich intercellular junctions and loss of adhesion. However, the potential role of ␣-catenin in directly modulating the adhesive function of individual E-cadherin molecules in human cancer is unknown. Here we use single-molecule force spectroscopy to probe the tensile strength, unstressed bond lifetime, and interaction energy between E-cadherins expressed on the surface of live human parental breast cancer cells lacking ␣-catenin and these cells where ␣-catenin is re-expressed. We find that the tensile strength and the lifetime of single E-cadherin/E-cadherin bonds between parental cells are significantly lower over a wide range of loading rates. Statistical analysis of the force displacement spectra reveals that single cadherin bonds between cancer cells feature an exceedingly low energy barrier against tensile forces and low molecular stiffness. Disassembly of filamentous actin using latrunculin B has no significant effect on the strength of single intercellular E-cadherin bonds. The absence of ␣-catenin causes a dominant negative effect on both global cell-cell adhesion and single E-cadherin bond strength. These results suggest that the loss of ␣-catenin alone drastically reduces the adhesive force between individual cadherin pairs on adjoining cells, explain the global loss of cell adhesion in human breast cancer cells, and show that the forced expression of ␣-catenin in cancer cells can restore both higher intercellular avidity and intercellular E-cadherin bond strength.The reduction of intercellular adhesion in a solid tumor is a critical step in the progression of tumor cells to metastasis (1). How normal cells lose their ability to form strong adhesions within a tissue is not well understood (2, 3). The loss of adhesion between adjoining epithelial cells and the ensuing onset of metastasis occur through an epithelial-to-mesenchymal transition that often correlates with the loss of cytoplasmic protein ␣-catenin and a poor prognosis in a wide range of cancers, including breast (4), esophageal (5), gastric (6, 7), cervical (8), and colorectal cancer (9). In normal epithelial tissues, ␣-catenin localizes to junctions that organize at the interface between adjacent epithelial cells through clustering of cell surface adhesion transmembrane molecule cadherin and its association to the cytoskeleton (10, 11). On the extracellular side, structural studies suggest that cadherin molecules form molecular pairs that interact with cadherin pairs on an adjacent cell through their distal Ca 2ϩ -binding domains (12). On the intracellular side, cadherin pairs are connected to the cytoskeleton network through specific linker proteins. Until recently it was believed that one critical linker protein between the cytoplasmic domain of cadherin and the actin cytoskeleton was ␣-catenin, because it can both bind filamentous actin (F-actin) and E-cadherin through ␤-catenin (13, 14). However, a recent study indicates tha...

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“…Decrease or loss of E-cadherin expression is a common feature of many human epithelial cancers, including cervical cancer, although a decreased expression of this molecule has been described in metastasis, but not primary tumours (Carico, 2001). It's widely accepted that hypermethylation plays a critical role in gene silencing.…”

Section: Expression Of E-cadherin In Cervical Cancermentioning

confidence: 99%

Evaluation of p53, p16INK4a and E-Cadherin Status as Biomarkers for Cervical Cancer Diagnosis

Mzibri¹,

Attaleb²,

Hassani³

et al. 2012

Topics on Cervical Cancer With an Advocacy for Prevention

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E-Cadherin and α-Catenin Expression during Tumor Progression of Cervical Carcinoma

Cited by 47 publications

References 27 publications

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

Loss of α-Catenin Decreases the Strength of Single E-cadherin Bonds between Human Cancer Cells

Evaluation of p53, p16INK4a and E-Cadherin Status as Biomarkers for Cervical Cancer Diagnosis

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