Abstract 6960: Lysosome inhibition suppress collective cell migration through caveolin-1 mediated E-cadherin stabilization in colon cancer cells

Abstract

Abstract In tumor nest growth and collective cell migration, the dynamics of E-cadherin is critical, and been shown to be regulated by cell vesicle traffic system. Caveolin-1 is the vesicle protein to regulate caveolae associated endocytosis, many of the membrane receptors are shown been regulated by caveolin-1 in cancer progression, however, the role is still controversial. This study demonstrated the effect of lysosome inhibition in caveolin-1 mediated E-cadherin turnover in the cell cohort of colon cancer cells. HT-29 colon cancer cells were used in this study, the cells were treated with chloroquine to inhibit lysosome activity. The cell spheroid from HT-29 cells were also collected according to cell adhesion ability. Caveolin-1 and E-cadherin were immuno-stained and revealed by confocal microscopy. In the result of immunostaining, caveolin-1 was showed the co-localization with E-cadherin at cell-cell contacts. When cells were treated with chloroquine, the lysosome inhibitor, the collective cell migration of HT-29 cells were suppressed, and stable caveolin-1 distribution was found accumulated on the cell-cell contacts., meanwhile, chloroquine has no effect on clathrin distribution at either cell-cell contacts or cell leading edge. Furthermore, the distribution of caveolin-1 at cell-cell contacts on cell spheroid that derived from HT-29 cells was decreased. The results of these study suggested lysosome plays important role in mediating caveolin-1 regulated E-cadherin dynamics in collective cell migration, but not in the cell spheroid formation. The results of these study demonstrated chloroquine can be the potential inhibitor for collective cell migration in colon cancer cells through caveolin-1 mediated vesicle transport. Citation Format: Yu-Chien Ching, Hui-Chun Chen, Yu-Chun Wang, Chun-Pu Cheng, Chia-En Ku, Shin-Ru Lee, Wei-Ting Chao. Lysosome inhibition suppress collective cell migration through caveolin-1 mediated E-cadherin stabilization in colon cancer cells [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 6960.