Dynamics of cell adhesion and motility in living cells is altered by a single amino acid change in E-cadherin fused to enhanced green fluorescent protein.

E-Cadherin regulates epithelial cell adhesion and is critical for the maintenance of tissue integrity. In sporadic diffuse-type gastric carcinoma, mutations of the E-cadherin gene are frequently observed that predominantly affect putative calcium binding motifs located in the linker region between the second and third extracellular domains. A single amino acid change (D370A) as found in a gastric carcinoma patient reduces cell adhesion and up-regulates cell motility.

Effect of wild-type and mutant E-cadherin on cell proliferation and responsiveness to the chemotherapeutic agents cisplatin, etoposide, and 5-fluorouracil.

Objectives: The cell adhesion molecule E-cadherin acts as a tumor and invasion suppressor and regulates cell proliferation. The aim of the present study was to investigate the impact of wild-type (wt) E-cadherin and tumor-derived mutant E-cadherin variants on the proliferation rate of MDA-MB-435S mammary carcinoma cells and the sensitivity of the cells to the chemotherapeutic drugs cisplatin, etoposide and 5-fluorouracil (5-FU) and whether p53 is involved in the chemotherapeutic response.

Methods: Proliferation rate was measured by XTT cell viability assay in the presence or absence of chemotherapeutics.

Motility enhancement by tumor-derived mutant E-cadherin is sensitive to treatment with epidermal growth factor receptor and phosphatidylinositol 3-kinase inhibitors.

Diffuse-type gastric and lobular breast cancers are characterized by frequent mutations in the cell adhesion molecule E-cadherin. Here we report that tumor-associated mutations of E-cadherin enhanced random cell movement of transfected MDA-MB-435S mammary carcinoma cells as compared to wild-type (wt) E-cadherin-expressing cells. The mutations included in frame deletions of exons 8 or 9 and a point mutation in exon 8 which all affect putative calcium-binding sites within the linker region of the second and third extracellular domain.