The NADPH oxidase NOX4 represses epithelial to amoeboid transition and efficient tumour dissemination.

ABSTRACT: Epithelial to mesenchymal transition is a common event during tumour dissemination. However, direct epithelial to amoeboid transition has not been characterized to date. Here we provide evidence that cells from hepatocellular carcinoma (HCC), a highly metastatic cancer, undergo epithelial to amoeboid transition in physiological environments, such as organoids or three-dimensional complex matrices. Furthermore, the NADPH oxidase NOX4 inhibits this transition and therefore suppresses efficient amoeboid bleb-based invasion. Moreover, NOX4 expression is associated with E-cadherin levels and inversely correlated with invasive features. NOX4 is necessary to maintain parenchymal structures, increase cell-cell and cell-to-matrix adhesion, and impair actomyosin contractility and amoeboid invasion.

SUBMITTER: Crosas-Molist E 

PROVIDER: S-EPMC5354266 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature