The E-cadherin (CDH1) gene, plays an intricate role in diffuse gastric cancer.
E-cadherin is a cell adhesion molecule that is encoded on chromosome 16, and is responsible for cell-to-cell adhesion between epithelial cells, forming a barrier between adjacent cells.
When E-cadherin is mutated, it allows cancer cells to invade previously impenetrable borders and can contribute to metastases.
The loss of E-cadherins has been implicated in gastric, colorectal, lobular breast, and ovarian cancers.
Involved in epithelial cell to cell interactions.
The gene mutated in HDGC, CDH1, codes for the E-Cadherin protein, which serves numerous functions in cell to cell interactions, as well as intracellular signaling.
Development of malignancy may be related to several of these functions: cell-cell adhesion facilitated by E-Cadherin binding.
Loss of this function may lead to dedifferentiation of cells and/or unregulated cell growth and replication.
Another major function includes binding and sequestering of the beta-catenin transcription factor, keeping it inactive.
Loss of this function may lead to overactivity of the transcription factor.
Cumulative risk for gastric cancer in CDH1 mutation carriers is 70% by 80 years for men and 56% for women.
Cumulative risk for breast cancer by 80 years is 42% for women with CDH1 mutations.
Associateied with invasive lobular carcinoma of the breast.
With a mutated CDH1 gene leading to an E-cadherin deficiency there is a greater than 80% chance of acquiring diffuse gastric cancer in their lifetime.
Patients with CDH1 gene gastric cancer typically present around age 40 years.
Patients with this known mutation are usually advised to have a total gastrectomy sometime between 20 and 40 years of age.
N-cadherin is expressed in regions of active remyelination and may play an important role in generating a local environment conducive to remyelination.
N-cadherin agonists have been identified and observed to stimulate neurite growth and cell migration, key aspects of promoting axon growth and remyelination after injury or disease.
At least five inherited CDH1 gene mutations have been identified in people with blepharocheilodontic (BCD) syndrome.
This disorder is present at birth and causes abnormalities mainly affecting the eyelids and mouth, including openings on both sides of the upper lip (bilateral cleft lip) and an opening in the roof of the mouth (cleft palate).
CDH1 gene mutations are thought to result in an abnormal E-cadherin protein that is quickly broken down, and impairs the interaction between E-cadherin and p120-catenin and affects craniofacial development, leading to the features of BCD syndrome.
Somatic CDH1 gene mutations are also associated with an increased risk of other cancers-endometrium, ovaries in women, and prostate cancer in men.
These CDH1 gene mutations are thought to result in a nonfunctional E-cadherin protein.
A loss of functional E-cadherin in these cells prevents tumor suppression and cell adhesion, leading to rapid cell growth and metastasis.
Individuals with inherited CDH1 gene mutations may have cleft lip, cleft palate, or both without the other signs and symptoms of BCD syndrome and with or without a family history of HDGC.
The CDH1 gene mutations in these individuals are thought to alter the E-cadherin protein and impair normal craniofacial development, leading to orofacial clefting.