A tale of two states: Normal and transformed, with and without rigidity sensing

For many years, major differences in morphology, motility, and mechanical characteristics have been observed between transformed cancer and normal cells. In this review, we consider these differences as linked to different states of normal and transformed cells that involve distinct mechanosensing and motility pathways. There is a strong correlation between repeated tissue healing and/or inflammation and the probability of cancer, both of which involve growth in adult tissues. Many factors are likely needed to enable growth, including the loss of rigidity sensing, but recent evidence indicates that microRNAs have important roles in causing the depletion of growth-suppressing proteins. One microRNA, miR-21, is overexpressed in many different tissues during both healing and cancer. Normal cells can become transformed by the depletion of cytoskeletal proteins that results in the loss of mechanosensing, particularly rigidity sensing. Conversely, the transformed state can be reversed by the expression of cytoskeletal proteins-without direct alteration of hormone receptor levels. In this review, we consider the different stereotypical forms of motility and mechanosensory systems. A major difference between normal and transformed cells involves a sensitivity of transformed cells to mechanical perturbations. Thus, understanding the different mechanical characteristics of transformed cells may enable new approaches to treating wound healing and cancer.