biostudies-literatureChen YHMinistry of EducationCancer Progression Research Center, National Yang Ming Chiao Tung UniversityNational Science and Technology Councile202201529https://www.ebi.ac.uk/biostudies/studies/S-EPMC9711860biostudies-literatureUnknown6(2)Epithelial cells usually trigger their "migratory machinery" upon loss of adhesion to their neighbors. This default is important for both physiological (e.g., wound healing) and pathological (e.g., tumor metastasis) processes. However, the underlying mechanism for such a default remains unclear. In this study, we used the human head and neck squamous cell carcinoma (HNSCC) SAS cells as a model and found that loss of cell-cell adhesion induced reactive oxygen species (ROS) generation and vimentin expression, both of which were required for SAS cell migration upon loss of cell-cell adhesion. We demonstrated that Tiam1-mediated Rac1 activation was responsible for the ROS generation through NADPH-dependent oxidases. Moreover, the ROS-Src-STAT3 signaling pathway that led to vimentin expression Life science allianceLoss of cell-cell adhesion triggers cell migration through Rac1-dependent ROS generation.PMC9711860108-2320-B-010-015-MY3Hsu JYChu CTChang YWYang MHChen HCFan JRChen YHfalseLoss of cell-cell adhesion triggers cell migration through Rac1-dependent ROS generation.Epithelial cells usually trigger their "migratory machinery" upon loss of adhesion to their neighbors. This default is important for both physiological (e.g., wound healing) and pathological (e.g., tumor metastasis) processes. However, the underlying mechanism for such a default remains unclear. In this study, we used the human head and neck squamous cell carcinoma (HNSCC) SAS cells as a model and found that loss of cell-cell adhesion induced reactive oxygen species (ROS) generation and vimentin expression, both of which were required for SAS cell migration upon loss of cell-cell adhesion. We demonstrated that Tiam1-mediated Rac1 activation was responsible for the ROS generation through NADPH-dependent oxidases. Moreover, the ROS-Src-STAT3 signaling pathway that led to vimentin expression 2023-01-01T00:00:00Z2023 Feb2025-04-26T09:39:57.625Z2025-04-06T13:08:38.952ZS-EPMC97118603644652410.26508/lsa.202201529