Structural basis of cell-cell adhesion by cadherins

Shapiro, Lawrence; Fannon, Allison M.; Kwong, Peter D.; Thompson, Andrew; Lehmann, M. S.; Grübel, G.; Legrand, J.F.; Als‐Nielsen, J.; Colman, David; Hendrickson, Wayne A.

doi:10.1038/374327a0

Cited by 1,101 publications

(1,026 citation statements)

References 44 publications

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“…Different strategies have been described to achieve anoikis resistance (Figure 4). A functional approach involves the modulation of the expression of cell adhesion molecules, such as integrins, which stabilize the normal cell-matrix contacts [77,78]. Indeed, a change in the pattern of integrin expression may influence the downstream signalling cascades to enhance cell survival.…”

Section: Anoikis Resistance In Cancermentioning

confidence: 99%

Anoikis: an emerging hallmark in health and diseases

Taddei

Giannoni

Fiaschi

et al. 2011

The Journal of Pathology

524

404

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Anoikis is a programmed cell death occurring upon cell detachment from the correct extracellular matrix, thus disrupting integrin ligation. It is a critical mechanism in preventing dysplastic cell growth or attachment to an inappropriate matrix. Anoikis prevents detached epithelial cells from colonizing elsewhere and is thus essential for tissue homeostasis and development. As anchorage-independent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are crucial steps during tumour progression and metastatic spreading of cancer cells, anoikis deregulation has now evoked particular attention from the scientific community. The aim of this review is to analyse the molecular mechanisms governing both anoikis and anoikis resistance, focusing on their regulation in physiological processes, as well as in several diseases, including metastatic cancers, cardiovascular diseases and diabetes.

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Section: Anoikis Resistance In Cancermentioning

confidence: 99%

Anoikis: an emerging hallmark in health and diseases

Taddei

Giannoni

Fiaschi

et al. 2011

The Journal of Pathology

524

404

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“…The density maps for long basal-link filaments are best matched by a tetramer, such as a cadherin (Shapiro et al 1995;Nagar et al 1996), comprising two dimers arranged side-by-side and joined head-to-head. Our data are compatible with a tetramer of cadherin 23, which extends 122 nm for a model including 27 extracellular ectodomains.…”

Section: Organization Of Basal Linksmentioning

confidence: 99%

Three-dimensional Architecture of Hair-bundle Linkages Revealed by Electron-microscopic Tomography

Auer

Koster

Ziese

et al. 2008

JARO

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The senses of hearing and balance rest upon mechanoelectrical transduction by the hair bundles of hair cells in the inner ear. Located at the apical cellular surface, each hair bundle comprises several tens of stereocilia and a single kinocilium that are interconnected by extracellular proteinaceous links. Using electron-microscopic tomography of bullfrog saccular sensory epithelia, we examined the three-dimensional structures of basal links, kinociliary links, and tip links. We observed significant differences in the appearances and dimensions of these three structures and found two distinct populations of tip links suggestive of the involvement of different proteins, splice variants, or protein-protein interactions. We noted auxiliary links connecting the upper portions of tip links to the taller stereocilia. Tip links and auxiliary links show a tendency to adopt a globular conformation when disconnected from the membrane surface.

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“…The mammalian cadherin superfamily is characterized by the presence of a unique domain called the cadherin motif or ectodomain (EC domain) (Gumbiner and Yamada, 1995;Shapiro et al, 1995). This family includes classic cadherins, protocadherins, desmogleins, desmocollins, cadherin-related neuronal receptors (CNRs), FATs, seven-pass transmembrane cadherins and Ret tyrosine kinase (Yagi and Takeichi, 2000;Angst et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation

Ying

Seng³

et al. 2005

Oncogene

247

288

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Protocadherins constitute the largest subgroup in the cadherin superfamily of cell adhesion molecules. Their major functions are poorly understood, although some are implicated in nervous system development. As tumorspecific promoter methylation is a marker for tumor suppressor genes (TSG), we searched for epigenetically inactivated TSGs using methylation-subtraction combined with pharmacologic demethylation, and identified the PCDH10 CpG island as a methylated sequence in nasopharyngeal carcinoma (NPC). PCDH10 is broadly expressed in all normal adult and fetal tissues including the epithelia, though at different levels. It resides at 4q28.3 -a region with hemizygous deletion detected by array-CGH in NPC cell lines; however, PCDH10 itself is not located within the deletion. In contrast, its transcriptional silencing and promoter methylation were frequently detected in multiple carcinoma cell lines in a biallelic way, including 12/12 nasopharyngeal, 13/16 esophageal, 3/4 breast, 5/5 colorectal, 3/4 cervical, 2/5 lung and 2/8 hepatocellular carcinoma cell lines, but not in any immortalized normal epithelial cell line. Aberrant methylation was further frequently detected in multiple primary carcinomas (82% in NPC, 42-51% for other carcinomas), but not normal tissues. The transcriptional silencing of PCDH10 could be reversed by pharmacologic demethylation with 5-aza-2 0 -deoxycytidine or genetic demethylation with double knockout of DNMT1 and DNMT3B, indicating a direct epigenetic mechanism. Ectopic expression of PCDH10 strongly suppressed tumor cell growth, migration, invasion and colony formation. Although the epigenetic and genetic disruptions of several classical cadherins as TSGs have been well documented in tumors, this is the first report that a widely expressed protocadherin can also function as a TSG that is frequently inactivated epigenetically in multiple carcinomas.

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Structural basis of cell-cell adhesion by cadherins

Cited by 1,101 publications

References 44 publications

Anoikis: an emerging hallmark in health and diseases

Anoikis: an emerging hallmark in health and diseases

Three-dimensional Architecture of Hair-bundle Linkages Revealed by Electron-microscopic Tomography

Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation

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