ABSTRACT Amoeboid behaviour represents a distinct and clinically significant cancer cell state within the epithelial-to-mesenchymal transition (EMT) spectrum. Defined by the loss of cell–cell junctions and adoption of a rounded morphology, amoeboid cancer cells exhibit low adhesion and rely heavily on Rho–ROCK–myosin II-mediated cortical contractility. This combination of high contractility and reduced adhesion enables rapid migration through dense, confining environments, using blebs as functional protrusions. This behaviour is commonly observed at tumour invasive fronts, within metastatic deposits and among therapy-resistant cell populations. Amoeboid identity integrates multiple biochemical signalling programmes alongside mechanical cues such as confinement, matrix topography and shear stress. Collectively, these factors drive a highly plastic state characterised by stem-cell-like traits, metabolic adaptability, low oxidative stress and an immunosuppressive secretome. Such features confer strong metastatic potential and broad resistance to therapy, underpinned by core physicochemical dependencies on cortical tension, membrane mechanics and redox balance. This Cell Science at a Glance article and the accompanying poster highlight these defining characteristics, establishing amoeboid behaviour as a crucial driver of cancer progression and an increasingly promising therapeutic target.
Ghose et al. (Fri,) studied this question.