Subcellular regulation of cancer cell mechanics

Cancer cells exhibit altered biophysical and biomechanical properties that contribute to an overall altered mechanical phenotype. Increasing evidence demonstrates that cancer cells are often associated with decreased bulk stiffness and higher contractility, properties that facilitate increased motility and invasiveness. These changes in cellular properties are most often due to subcellular alterations in the cytoskeletal organization that results from both changes in intracellular regulators as well as changes to the tumor microenvironment. This review will highlight recent key findings describing the role of upregulated cytoskeletal scaffolding proteins and signaling circuits, as well as microenvironmental cues that influence cytoskeletal regulation and epithelial-to-mesenchymal transition to alter cancer cell stiffness and contractility. We also briefly discuss the emerging role of extracellular microvesicles in long-range cell-cell modulation of cytoskeletal mechanics and malignant transformation.