CDH6

Official Full Name

cadherin 6

Organism

Homo sapiens

GeneID

1004

Background

This gene encodes a member of the cadherin superfamily. Cadherins are membrane glycoproteins that mediate homophilic cell-cell adhesion and play critical roles in cell differentiation and morphogenesis. The encoded protein is a type II cadherin and may play a role in kidney development as well as endometrium and placenta formation. Decreased expression of this gene may be associated with tumor growth and metastasis. [provided by RefSeq, May 2011]

Synonyms

CAD6; KCAD;

Protein Sequence

MRTYRYFLLLFWVGQPYPTLSTPLSKRTSGFPAKKRALELSGNSKNELNRSKRSWMWNQFFLLEEYTGSDYQYVGKLHSDQDRGDGSLKYILSGDGAGDLFIINENTGDIQATKRLDREEKPVYILRAQAINRRTGRPVEPESEFIIKIHDINDNEPIFTKEVYTATVPEMSDVGTFVVQVTATDADDPTYGNSAKVVYSILQGQPYFSVESETGIIKTALLNMDRENREQYQVVIQAKDMGGQMGGLSGTTTVNITLTDVNDNPPRFPQSTYQFKTPESSPPGTPIGRIKASDADVGENAEIEYSITDGEGLDMFDVITDQETQEGIITVKKLLDFEKKKVYTLKVEASNPYVEPRFLYLGPFKDSATVRIVVEDVDEPPVFSKLAYILQIREDAQINTTIGSVTAQDPDAARNPVKYSVDRHTDMDRIFNIDSGNGSIFTSKLLDRETLLWHNITVIATEINNPKQSSRVPLYIKVLDVNDNAPEFAEFYETFVCEKAKADQLIQTLHAVDKDDPYSGHQFSFSLAPEAASGSNFTIQDNKDNTAGILTRKNGYNRHEMSTYLLPVVISDNDYPVQSSTGTVTVRVCACDHHGNMQSCHAEALIHPTGLSTGALVAILLCIVILLVTVVLFAALRRQRKKEPLIISKEDIRDNIVSYNDEGGGEEDTQAFDIGTLRNPEAIEDNKLRRDIVPEALFLPRRTPTARDNTDVRDFINQRLKENDTDPTAPPYDSLATYAYEGTGSVADSLSSLESVTTDADQDYDYLSDWGPRFKKLADMYGGVDSDKDS

Open

Disease

Ovarian cancer

Approved Drug

Clinical Trial Drug

1 +

Discontinued Drug

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Detailed Information

CDH6, also known as Cadherin 6 or K-Cadherin, is a gene that encodes a single-pass transmembrane protein located at the basolateral membrane of epithelial cells. Crucially important for epithelial cell differentiation and morphogenesis, this protein facilitates homophilic cell-cell adhesion via a calcium-dependent mechanism. Unlike other cadherins, CDH6 is a type II classic cadherin devoid of the extracellular N-terminal region common in type I cadherins. Rather, it has a unique extracellular sticky domain that, by homologous molecular interaction, maintains persistent cell-cell attachment.

In normal physiological settings, CDH6 expression is limited to certain tissues, including renal tubular cells and bile duct epithelial cells, where it is engaged in cell-cell interactions helping to maintain cellular polarity and organ function. Additionally, CDH6 plays a key role during embryonic development, particularly in the formation of the endometrium and placenta, as well as in kidney development.

CDH6 and Its Association with Tumors

Although CDH6 is usually expressed in low quantities in adult tissues, its overexpression is clearly shown in some malignant tumors, including renal cell carcinoma (RCC) and ovarian cancer (OVC). Research on CDH6 expression in these tumors reveals that its level is favorably linked with tumor aggressiveness and metastatic potential whereas its expression connects with malignant characteristics.

Between 65% and 85% of patients with ovarian cancer have CDH6 overexpression. A major component of tumor cells' ability to detach from their initial place and enter the bloodstream or lymphatic system is thought to be the high expression of CDH6, therefore enabling cancer cell metastasis. In RCC, too, CDH6 is regarded as a possible biomarker as its overexpression is tightly correlated with tumor development and metastases.

Not only can the overexpression of CDH6 improve tumor invasiveness but it may also cause tight cell-cell junctions to be disrupted, enabling cancer cells to penetrate nearby tissues and cause metastases. CDH6 is thus seen as a possible therapeutic target for cancer therapy.

The Role of CDH6 in Disease

Different disorders have been linked to unusual expression of CDH6. Apart from cancers, CDH6 is linked to other hereditary diseases and developmental abnormalities. For Craniofacial-Deafness-Hand Syndrome, for instance, loss of CDH6 function is thought to be a major contributor to the syndrome's expression. Moreover, the function of CDH6 in cell-cell adhesion makes it crucial in renal development and endocrine disorders.

The contrast between the restricted expression of CDH6 in normal kidney tissue and its overexpression in RCC emphasizes the important part the gene plays in kidney cell differentiation, function preservation, and tumor development. Proposed to be important in the development of various malignancies including ovarian, breast, and lung tumors is an excessive expression of CDH6.

Clinical Applications and Future Prospects

Given the great expression of CDH6 in many malignancies, especially in ovarian and renal cell carcinomas, CDH6 is considered a possible tumor marker. Particularly in the formulation of antibody-drug conjugates (ADCs), targeted therapeutics targeting CDH6 have attracted a lot of interest. By connecting them to certain targeting antibodies, ADCs are meant to deliver chemotherapeutic medications straight to tumor cells. Given the great selectivity of CDH6 expression in many cancers, ADC medication research has found a suitable target in this regard.

Therapeutic methods aiming at CDH6 also include small-molecule drug development and gene therapy. These approaches have potential in early cancer detection and therapy. Small compounds or gene therapy may help to either restore or suppress CDH6 expression, therefore slowing down tumor development and effectively lowering tumor cell invasiveness.

References:

Giroldi LA, Shimazui T, Schalken JA, et al. Classical cadherins in urological cancers. Morphologie. 2000 Jun;84(265):31-8.
MacCalman CD, Getsios S, Chen GT. Type 2 cadherins in the human endometrium and placenta: their putative roles in human implantation and placentation. Am J Reprod Immunol. 1998 Feb;39(2):96-107.
Gugnoni M, Sancisi V, Gandolfi G, Manzotti G, Ragazzi M, Giordano D, Tamagnini I, Tigano M, Frasoldati A, Piana S, Ciarrocchi A. Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy. Oncogene. 2017 Feb 2;36(5):667-677.

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