Abstract 304: The role of DDR1 mediated E-cadherin stability in collective colon cancer cell migration

Abstract

Abstract In cancer metastasis, the mechanism of single cell migration and collective cell migration are investigated. The dynamics of E-cadherin is critical in collective cell migration as the important mechanism of metastasis. DDR1 (Discoidin Domain Receptor 1) has been shown to promote E-cadherin stability at adherens junction in epithelial cells by regulating endocytosis of E-cadherin. However, in the growth of epithelial cell cluster and collective cell migration, the role of DDR1 in the cell-cell contacts is not clear. In this study, HT-29 colon cancer cells with epithelial phenotype were used in the experiments. Cells were treated with epidermal growth factor to stimulate E-cadherin turnover or applied with lysosome inhibitor chloroquine to interfere cellular vesicle transport. DDR1 and E-cadherin were revealed by immuno-confocal microscopy. The immunostaining results showed DDR1 was localized at cell-cell contacts and co-localized with E-cadherin. When cells were treated with epidermal growth factor, the phosphor MAPK activity was increased and DDR1 was localized at cell-cell contacts intensively. When lysosome activity was blocked by chloroquine treatment. The cellular vesicle transport and collective cell migration was reduced and furthermore inhibited DDR1 translocation to the cell-cell contacts. This study demonstrated DDR1 co-localized with E-cadherin is responsible for epidermal growth factor stimulation in cell cohort. Lysosome activity is required for E-cadherin turnover and affected DDR1 translocation. Chloroquine maybe the potential drug to suppress tumor nest growth and collective cell migration by interfere DDR1 mediated E-cadherin stability. Citation Format: Hui-Chun Chen, Yu-Chun Wang, Yu-Chien Ching, Chun-Pu Cheng, Chia-En Ku, Shin-Ru Lee, Wei-Ting Chao. The role of DDR1 mediated E-cadherin stability in collective colon cancer cell migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 304.