The microenvironment and cytoskeletal remodeling in tumor cell invasion

The physical cues of tumor microenvironment (TME) contribute greatly to the initiation and progression of cancer. Tumor tissues usually become stiffer than healthy tissues with more aligned fibers and changed porosity. In recent years, numerous studies attempted to investigate whether biophysical cues from the surrounding environment affect the biophysical, biochemical, and biological behavior of cells and consequently attribute to the development of cancer. Here, we review recent advances of our understanding of these physical cues in terms of extracellular matrix (ECM) stiffness and topography (alignment and porosity). We discuss the underlying mechanisms of changes in TME physical parameters. Then, we summarize how cancer cells sense the mechanical signals, transfer them to the downstream signaling pathways, and finally translate them to different cellular behaviors. Specifically, we discuss the role of mechanical changes of ECM in cancer cell stiffness, actin cytoskeleton organization, gene and protein expressions, the migration of cancer cells, and their response to specific treatments. We then review different methods which have been successfully utilized to model ECM physical properties. This review paper concluded with the limitations of current studies which followed by some insights into clarifying the therapeutic potential of ECM mechanical properties to target and control the development of cancer.