Cadherin Cell Adhesion Receptors as a Morphogenetic Regulator

Takeichi, Masatoshi

doi:10.1126/science.2006419

Cited by 3,104 publications

(2,124 citation statements)

References 53 publications

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“…Recent studies have described overexpression of two proto-oncogenes, pituitary tumor trans- [26][27][28] Because cell discohesiveness and detachment are important for tumor invasiveness, loss or downregulated expression of H-cadherin and E-cadherin may facilitate tumor invasion. 2,29,30 Furthermore, E-cadherin also has a growth suppressor function by inducing cell-cycle arrest via upregulation of the cyclin-dependent kinase inhibitor p27. 31 In this study, reduced expression of the CDH13 gene was also associated with tumor aggressiveness (84% invasive cases vs 38% non-invasive cases in qRT-PCR analysis).…”

Section: Discussionmentioning

confidence: 99%

Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas

et al. 2007

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The gene products of CDH13 and CDH1, H-cadherin and E-cadherin, respectively, play a key role in cell-cell adhesion. Inactivation of the cadherin-mediated cell adhesion system caused by aberrant methylation is a common finding in human cancers, indicating that the CDH13 and CDH1 function as tumor suppressor and invasion suppressor genes. In this study, we analyzed the expression of H-cadherin mRNA and E-cadherin protein in 5 normal pituitary tissues and 69 primary pituitary adenomas including all major types by quantitative real-time RT-PCR (qRT-PCR) and immunohistochemistry, respectively. Reduced expression of H-cadherin was detected in 54% (28/52) of pituitary tumors and was significantly associated with tumor aggressiveness (Po0.05). E-cadherin expression was lost in 30% (21 of 69) and significantly reduced in 32% (22 of 69) of tumors. E-cadherin expression was significantly lower in grade II, III, and IV than in grade I adenomas (P ¼ 0.015, P ¼ 0.029, and P ¼ 0.01, respectively). Using methylation-specific PCR (MSP), promoter hypermethylation of CDH13 and CDH1 was detected in 30 and 36% of 69 adenomas, respectively, but not in 5 normal pituitary tissues. Methylation of CDH13 was observed more frequently in invasive adenomas (42%) than in non-invasive adenomas (19%) (Po0.05) and methylation of CDH1 was more frequent in grade IV adenomas compared with grade I adenomas (Po0.05). Methylation of either CDH13 or CDH1 was identified in 35 cases (51%) and was more frequent in grade IV invasive adenomas than in grade I non-invasive adenomas (Po0.05 and Po0.05, respectively). Downregulation of expression was correlated with promoter hypermethylation in CDH13 and CDH1. In conclusion, the tumor-specific downregulation of expression and methylation of CDH13 and CDH1, alone or in combination, may be involved in the development and invasive growth of pituitary adenomas.

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Section: Discussionmentioning

confidence: 99%

Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas

et al. 2007

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“…b-Catenin is localized to cell-cell junctions by interaction with the cytoplasmic tail of a transmembrane protein E-cadherin. The E-cadherin/ b-catenin complex plays a crucial role in epithelial cellcell interaction and in the maintenance of the normal architecture of epithelial tissues (Takeichi, 1991). This complex also plays a role in canonical Wnt signaling, which regulates growth and differentiation of many cell types (Wang and Wynshaw-Boris, 2004).…”

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells

et al. 2007

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Infection with Helicobacter pylori cagA-positive strains is associated with gastric adenocarcinoma. Intestinal metaplasia is a precancerous lesion of the stomach characterized by transdifferentiation of the gastric mucosa to an intestinal phenotype. The H. pylori cagA gene product, CagA, is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases. Tyrosine-phosphorylated CagA specifically binds to and activates SHP-2 phosphatase, thereby inducing cell-morphological transformation. We report here that CagA physically interacts with E-cadherin independently of CagA tyrosine phosphorylation. The CagA/E-cadherin interaction impairs the complex formation between E-cadherin and b-catenin, causing cytoplasmic and nuclear accumulation of b-catenin. CagA-deregulated b-catenin then transactivates b-catenin-dependent genes such as cdx1, which encodes intestinal specific CDX1 transcription factor. In addition to b-catenin signal, CagA also transactivates p21 WAF1/Cip1 , again, in a phosphorylation-independent manner. Consequently, CagA induces aberrant expression of an intestinal-differentiation marker, goblet-cell mucin MUC2, in gastric epithelial cells that have been arrested in G1 by p21 WAF1/Cip1 . These results indicate that perturbation of the E-cadherin/b-catenin complex by H. pylori CagA plays an important role in the development of intestinal metaplasia, a premalignant transdifferentiation of gastric epithelial cells from which intestinal-type gastric adenocarcinoma arises.

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“…At ZA as well as cell ± cell AJ in nonepithelial cells, cadherin interacts with each other at the extracellular surface and serves as a critical adhesion molecule (Takeichi, 1988(Takeichi, , 1991Geiger and Ginsberg, 1991;Tsukita et al, 1992). b-and g-Catenins interact with the cytoplasmic region of cadherin, and a-catenin interacts with b-catenin (Ozawa et al, 1989;Nagafuchi et al, 1991;Takeichi, 1991;Tsukita et al, 1992;Aberle et al, 1996). Of these proteins, a-catenin interacts with F-actin (Rimm et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Different behavior of l-Afadin and Neurabin-II during the formation and destruction of cell – cell adherens junction

et al. 1999

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We have recently isolated two novel actin ®lament-binding proteins, l-afadin and neurabin-II and shown that they are localized at cell ± cell adherens junction (AJ) in epithelial cells. We found here that l-afadin, neurabin-II, ZO-1, and E-cadherin showed similar and di erent behavior during the formation and destruction of cell ± cell AJ in MDCK cells. In MDCK cells, the accumulation of both l-afadin and E-cadherin, but not that of ZO-1, changed in parallel depending on Rac small G protein activity. Dissociation of MDCK cells by culturing the cells at 2 mM Ca 2+ caused rapid endocytosis of E-cadherin, but not that of l-afadin or ZO-1. Addition of phorbol 12-myristate 13-acetate to these dissociated cells formed a tight junction-like structure where ZO-1 and l-afadin, but not neurabin-II or E-cadherin, accumulated. We furthermore found that, in nonepithelial EL cells, which expressed E-cadherin and attached to each other, l-afadin, neurabin-II, ZO-1 and E-cadherin were all localized at AJ. In cadherin-de®cient L cells, l-afadin was mainly localized at cell ± cell contact sites, but ZO-1 was mainly localized at the tip area of cell processes. Neurabin-II did not accumulate at the plasma membrane area. Neither l-afadin nor neurabin-II signi®cantly interacted with a-, b-catenin, E-cadherin, ZO-1 or occludin.

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Cadherin Cell Adhesion Receptors as a Morphogenetic Regulator

Cited by 3,104 publications

References 53 publications

Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas

Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas

Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells

Different behavior of l-Afadin and Neurabin-II during the formation and destruction of cell – cell adherens junction

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