Definition: The cadherin gene family encode proteins that mediate calcium-ion-dependent adhesion (calcium-dependent transmembrane adhesion molecules).

Cadherins (CDHs) are the principal components of AJs and desmosomes, and cluster at sites of cell-cell contact in most solid tissues. The cadherin superfamily consists of classical cadherins, which are the main mediators of calcium-dependent cell-cell adhesion, and non-classical cadherins, which include desmosomal cadherins and the recently discovered large subfamily of protocadherins, which are implicated in neuronal plasticity. The functional role of non-classical cadherins in tumour progression is unknown, so in this review we will focus on classical cadherins.

The name cadherin is derived from the term "calcium-dependent adherence protein." This family contains almost 90 members, which, as mentioned, participate in interaction between cells of the same type.

Cadherins (CDHs) are generally involved in calcium-dependent homotypic interactions, while immunoglobulin family CAMs, because of the types of ligands they can bind, participate in both homotypic and heterotypic cell-to-cell interactions. The integrins have broader ligand specificity and are responsible for many events involving cell adhesion.

These interactions connect the plasma membrane of adjacent cells, forming two types of cell junctions called (1) zonula adherens, small, spotlike junctions located near the apical surface of epithelial cells; and (2) desmosomes, stronger and more extensive junctions, present in epithelial and muscle cells. Linkage of cadherins with the cytoskeleton occurs through two classes of catenins (CTNNs).

These interactions connect the plasma membrane of adjacent cells, forming two types of cell junctions called (1) zonula adherens, small, spotlike junctions located near the apical surface of epithelial cells; and (2) desmosomes, stronger and more extensive junctions, present in epithelial and muscle cells. Linkage of cadherins with the cytoskeleton occurs through two classes of catenins (CTNNs).

?-catenin (CTNNB1) links cadherins with ?-catenin, which, in turn, connects to actin, thus completing the connection with the cytoskeleton.

Cell-to-cell interactions mediated by cadherins (CDHs) and catenins (CTNNs) play a major role in regulating cell motility, proliferation, and differentiation and account for the inhibition of cell proliferation that occurs when cultured normal cells contact each other (contact inhibition).

Proprotein convertases (PCs) and cadherins (CDHs)

Cadherins are a family of intercellular adhesion receptors. Produced as inactive precursors, they become functional adhesion molecules after proteolytic cleavage by subtilisin-like proprotein convertases (PCs).

Owing to their activation and assembly into multiprotein adhesion complexes at sites of cell contacts, adhesion-competent cadherins are prerequisite for tissue integrity.

Intercellular junctions not only provide mechanical linkage, but in addition are potent modulators of signalling cascades. This infers a biological role to intercellular adhesion complexes that is significantly more complex and powerful.

Members

CDH1	CDH2	CDH3	CDH4	CDH5	CDH6	CDH7	CDH8	CDH9	CDH10
CDH11	CDH12	CDH13	CDH14	CDH15	CDH16	CDH17	CDH18	CDH19	CDH20
CDH21	CDH22	CDH23

 E-cadherin ou cadherin-1 (CDH1) (MIM.192090)
 N-cadherin ou cadherin-2 (CDH2)
 P-cadherin ou cadherin-3 (CDH3) (MIM.114021)
 desmosomal cadherins

• desmogleins
• desmocollins

See also

 cadherin-mediated cell-cell adhesion
 cadherin-associated proteins

Pathology

 CDH1 (E-cadherin)

• reduced expression of E-cadherin in cancer invasion and metastasis trigger
• somatic mutations in
  • endometrial carcinoma
  • ovarian carcinoma
  • mammary lobular carcinoma

• constitutional mutations in autosomal dominant familial gastric cancer (MIM.137215)
• constitutional mutations in susceptibility to Listeria monocytogenes

 CDH3

• constitutional mutations of CDH3 in hypotrichosis with juvenile macular dystrophy (MIM.601553)

 CDH23

• mutations in the Usher disease type 1C
• mutations in the Usher disease type 1D (MIM.601067)
• mutations in the DFNB12 nonsyndromic autosomal recessive deafness (MIM.601386)

CDHs and cancer

 Loss of cadherins can favor the malignant phenotype by allowing easy disaggregation of cells, which can then invade locally or metastasize.
 Reduced cell-surface expression of E-cadherin has been noted in many types of cancers, including those that arise in the esophagus, colon, breast, ovary, and prostate.
 Germ line mutations of the E-cadherin gene can predispose to familial gastric carcinoma, and mutation of the gene and decreased E-cadherin expression are present in a variable proportion of gastric cancers of the diffuse type.
 The molecular basis of reduced E-cadherin expression is varied. In a small proportion of cases, there are mutations in the E-cadherin gene (located on 16q); in other cancers, E-cadherin expression is reduced as a secondary effect of mutations in ?-catenin genes.
 ?-catenins, as discussed earlier, bind to the intracellular portion of cadherins and stabilize their expression.

References

 Junghans D, Haas IG, Kemler R. Mammalian cadherins and protocadherins: about cell death, synapses and processing. Curr Opin Cell Biol. 2005 Oct;17(5):446-52. PMID: #16099637#

 Cowin P, Rowlands TM, Hatsell SJ. Cadherins and catenins in breast cancer. Curr Opin Cell Biol. 2005 Oct;17(5):499-508. PMID: #16107313#

 Bershadsky A. Magic touch: how does cell-cell adhesion trigger actin assembly? Trends Cell Biol. 2004 Nov;14(11):589-93. PMID: #15519846#

 Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer. 2004 Feb;4(2):118-32. PMID: #14964308#

 Tepass U, Truong K, Godt D, Ikura M, Peifer M. Cadherins in embryonic and neural morphogenesis. Nat Rev Mol Cell Biol. 2000 Nov;1(2):91-100. PMID: #11253370#

 Furukawa F, Takigawa M, Matsuyoshi N, Shirahama S, Wakita H, Fujita M, Horiguchi Y, Imamura S. Cadherins in cutaneous biology. J Dermatol. 1994 Nov;21(11):802-13. PMID: #7852640#