Loss of Myo19 increases metastasis by enhancing microenvironmental ROS gradient and chemotaxis.

ABSTRACT: Tumor metastasis involves cells migrating directionally in response to external chemical signals. Reactive oxygen species (ROS) in the form of H₂O₂ has been demonstrated as a chemoattractant for neutrophils but its spatial characteristics in tumor microenvironment and potential role in tumor cell dissemination remain unknown. Here we investigate the spatial ROS distribution in 3D tumor spheroids and identify a ROS concentration gradient in spheroid periphery, which projects into a H₂O₂ gradient in tumor microenvironment. We further reveal the role of H₂O₂ gradient to induce chemotaxis of tumor cells by activating Src and subsequently inhibiting RhoA. Finally, we observe that the absence of mitochondria cristae remodeling pro

SUBMITTER: Ren X 

PROVIDER: S-EPMC10933354 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature