Cadherin

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Cadherin-1 is a protein that in humans is encoded by the CDH1 gene.[1]

CDH1 has also been designated as CD324 (cluster of differentiation 324).

It is a tumor suppressor gene.[2][3]

 

This gene is a classical cadherin from the cadherin superfamily.

The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region, and a highly conserved cytoplasmic tail.

Mutations in this gene are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers.

Loss of function is thought to contribute to progression in cancer by increasing proliferation, invasion, and/or metastasis.

The ectodomain of this protein mediates bacterial adhesion to mammalian cells, and the cytoplasmic domain is required for internalization. Identified transcript variants arise from mutation at consensus splice sites.[4]

 

E-cadherin (epithelial) is the most well-studied member of the cadherin family.

It consists of 5 cadherin repeats (EC1 ~ EC5) in the extracellular domain, one transmembrane domain, and an intracellular domain that binds p120-catenin and beta-catenin.

The intracellular domain contains a highly-phosphorylated region vital to beta-catenin binding and, therefore, to E-cadherin function.[citation needed] Beta-catenin can also bind to alpha-catenin.

Alpha-catenin participates in regulation of actin-containing cytoskeletal filaments. In epithelial cells, E-cadherin-containing cell-to-cell junctions are often adjacent to actin-containing filaments of the cytoskeleton.

E-cadherin is first expressed in the 2-cell stage of mammalian development, and becomes phosphorylated by the 8-cell stage, where it causes compaction.[citation needed] In adult tissues, E-cadherin is expressed in epithelial tissues, where it is constantly regenerated with a 5-hour half-life on the cell surface.[citation needed]

Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis.[citation needed]

E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility.[citation needed]

This in turn may allow cancer cells to cross the basement membrane and invade surrounding tissues.

E-cadherin is also used by pathologists to diagnose different kinds of breast cancer.

When compared with invasive duct carcinoma, E-cadherin expression is markedly reduced or absent in the great majority of invasive lobular carcinomas when studied by immunohistochemistry.[5]

 

Contents

Interactions

CDH1 (gene) has been shown to interact with Beta-catenin,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] C-Met,[6] HDAC1,[29] Histone deacetylase 2,[29] FOXM1,[30] CTNND1,[31][32][10][12][33][17][24][34] CDH3,[35] IQGAP1,[36] CDC27,[37] FYN,[17] Plakoglobin,[10][12][38][39][40] CDON,[18] Vinculin,[9][12] Catenin (cadherin-associated protein), alpha 1[10][19][20][21][27] and NEDD9.[41]

 

See also

  • Cluster of differentiation

References

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 Further reading

  • Berx G, Becker KF, Höfler H, van Roy F (1998). "Mutations of the human E-cadherin (CDH1) gene.". Hum. Mutat. 12 (4): 226–37. doi:10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D. PMID 9744472. 
  • Wijnhoven BP, Dinjens WN, Pignatelli M (2000). "E-cadherin-catenin cell-cell adhesion complex and human cancer.". The British journal of surgery 87 (8): 992–1005. doi:10.1046/j.1365-2168.2000.01513.x. PMID 10931041. 
  • Beavon IR (2000). "The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation.". Eur. J. Cancer 36 (13 Spec No): 1607–20. doi:10.1016/S0959-8049(00)00158-1. PMID 10959047. 
  • Wilson PD (2001). "Polycystin: new aspects of structure, function, and regulation.". J. Am. Soc. Nephrol. 12 (4): 834–45. PMID 11274246. 
  • Chun YS, Lindor NM, Smyrk TC, et al. (2001). "Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?". Cancer 92 (1): 181–7. doi:10.1002/1097-0142(20010701)92:1<181::AID-CNCR1307>3.0.CO;2-J. PMID 11443625. 
  • Hazan RB, Qiao R, Keren R, et al. (2004). "Cadherin switch in tumor progression.". Ann. N. Y. Acad. Sci. 1014: 155–63. doi:10.1196/annals.1294.016. PMID 15153430. 
  • Bryant DM, Stow JL (2005). "The ins and outs of E-cadherin trafficking.". Trends Cell Biol. 14 (8): 427–34. doi:10.1016/j.tcb.2004.07.007. PMID 15308209. 
  • Wang HD, Ren J, Zhang L (2004). "CDH1 germline mutation in hereditary gastric carcinoma.". World J. Gastroenterol. 10 (21): 3088–93. PMID 15457549. 
  • Reynolds AB, Carnahan RH (2005). "Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer.". Semin. Cell Dev. Biol. 15 (6): 657–63. doi:10.1016/j.semcdb.2004.09.003. PMID 15561585. 
  • Moran CJ, Joyce M, McAnena OJ (2005). "CDH1 associated gastric cancer: a report of a family and review of the literature.". Eur J Surg Oncol 31 (3): 259–64. doi:10.1016/j.ejso.2004.12.010. PMID 15780560. 
  • Georgolios A, Batistatou A, Manolopoulos L, Charalabopoulos K (2006). "Role and expression patterns of E-cadherin in head and neck squamous cell carcinoma (HNSCC).". J. Exp. Clin. Cancer Res. 25 (1): 5–14. PMID 16761612. 
  • Renaud-Young M, Gallin WJ (2002). "In the first extracellular domain of E-cadherin, heterophilic interactions, but not the conserved His-Ala-Val motif, are required for adhesion". Journal of Biological Chemistry 277 (42): 39609–39616. doi:10.1074/jbc.M201256200. PMID 12154084. 

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