Two Regions of Cadherin Cytoplasmic Domains Are Involved in Suppressing Motility of a Mammary Carcinoma Cell Line

• Published in: The Journal of biological chemistry Vol. 278; no. 52; pp. 52371 - 52378
• Main Authors: Fedor-Chaiken, Mary, Meigs, Thomas E., Kaplan, Daniel D., Brackenbury, Robert
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.12.2003; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; b-catenin; beta Catenin; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cadherins - chemistry; Cadherins - genetics; Cell Line, Tumor; Cell Movement; Cytoplasm - metabolism; Cytoskeletal Proteins - metabolism; Gene Deletion; Genetic Vectors; Humans; Immunoblotting; Mice; Molecular Sequence Data; Mutation; Precipitin Tests; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Subcellular Fractions; Time Factors; Trans-Activators - metabolism; Wound Healing
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M310576200

E-cadherin has been termed an “invasion suppressor,” yet the mechanism of this suppression is not known. In contrast, several reports indicate N-cadherin does not suppress but, rather, promotes cell motility and invasion. Here, by characterizing a series of chimeric cadherins we defined a previously uncharacterized region consisting of the transmembrane domain and an adjacent portion of the cytoplasmic segment that is responsible for the difference in ability of E- and N-cadherin to suppress movement of mammary carcinoma cells, as quantified from time-lapse video recordings. A mutation in this region enabled N-cadherin to suppress motility, indicating that both E- and N-cadherin can suppress, but the activity of N-cadherin is latent, presumably repressed by binding of a specific inhibitor. To define regions common to E- and N-cadherin that are required for suppression, we analyzed a series of deletion mutants. We found that suppression of movement requires E-cadherin amino acids 699–710. Strikingly, β-catenin binding is not sufficient for and p120ctn is not involved in suppression of these mammary carcinoma cells. Furthermore, the comparable region of N-cadherin can substitute for this required region in E-cadherin and is required for suppression by the mutant form of N-cadherin that is capable of suppressing. Variations in expression of factors that bind to the two regions we have identified may explain previously observed differences in response of tumor cells to cadherins.