The cadherins establish molecular links between adjacent cells by means "zipper-like structures" at membrane regions where a cell makes contact with other cells. Thus cadherins are essential to the architecture of the body; without them cells could not aggregate into larger structures, such as organs.
The expression of cadherin molecules in the embryo is crucial for the migration of cells and the differentiation of tissues. As one might expect, cadherins are crucial for the maintenance of epithelial structure -One can imagine what loss of epithelial cell to cell adhesion would be like. It can be similar to losing the glue that holds the epithelial cells together.
Since cancer cells tend to spread by losing their ability to adhere to their base tissue, not surprisingly, cadherins are the subject of considerable study with regard to cancer metastasis. The initial step of cancer metastasis is the detachment of cells from the primary tumor mass. In tumors of epithelial origin, the loss of cadherin's self-adherence function is directly proportional to the probability that that tumor will metastasize. Indeed, under normal conditions with sufficient activity of cadherins, cells are unable to disrupt their mutual connections; only in the state of cadherin inactivation may a cells be freed from its adhesive constraints and migrate out of its parent colonies. In fact reduced cadherin levels have been observed in a broad range of malignancies, including cancers of the head and neck, lung, breast, prostate, oesophagus, stomach and colorectum. Clinical studies suggest that the loss of E-cadherin function is directly associated with tumor invasion and metastasis. In gastric carcinoma, highly differentiated tumors generally maintain homogeneous, strong expression of cadherin, while in more invasive tumors cadherin expression is found to be altered or even completely suppressed.
Cadherins mediate cell adhesion and play a fundamental role in normal development. They participate in the maintenance of proper cell-cell contacts.
E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule. The loss of E-cadherin expression may be involved in regional lymph node metastasis and in malignant potential of thyroid neoplasms. (
The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications
Cell Res. 2004 Oct ;14:423-33 Fei Geng, Bi Zhi Shi, Yun Feng Yuan, Xing Zhong Wu
It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E-cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since alpha-1,6 Fucosyltransferase (alpha-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by alpha-1,6 FucT targeted RNAi and transfecting alpha-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E-cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after alpha-1,6 FucT over expression. Our data indicated that alpha-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asymmetry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.