Fig. 1. The anchorage-independent survival and cellular and environmental changes during detachment.

After losing anchorage to ECM, the cells are exposed to a totally different environment and present multiple cellular changes, including disruption of extracellular matrix (ECM)–cell interaction, altered mechanical force, cytoskeleton reorganization, ATP deficiency, reduced nutrient uptake, and increased reactive oxygen species (ROS) production. A Disruption of extracellular matrix (ECM)–cell interaction. Integrins lose the binding of ligands and stimulation from the ECM. B Altered mechanical force. The main mechanical force shifts from ECM stiffness to fluid shear stress. C Cytoskeleton reorganization. The cells present a round cell morphology and the membrane proteins undergo structure deformation and activation. D ATP deficiency. ATP deficiency is a result of reduced ATP production, increased ATP release, and enhanced ATP consumption. E Reduced nutrient uptake. The uptake of glucose, glutamine, and pyruvate is reduced in detached cells due to various reasons. F Increased ROS production. The ROS generation is increased during detachment. As a result, the detached cells undergo anoikis, autophagy, entosis, and cell cycle arrest.