Does preserving normal tissue tensional homeostasis reduce the risk of malignant transformation?
Cells and tissues maintain a dynamic mechanical balance among the cytoskeleton, cell junctions, extracellular matrix, and nucleus. This organization is sometimes described as cellular or tissue tensegrity. Cancer is associated with profound disruption of this mechanical balance. Experimental evidence shows that altered cytoskeletal tension can influence cell fate, while abnormal extracellular-matrix stiffening can promote mechanotransduction, proliferation, invasion, and malignant behavior. Importantly, greater mechanical strength is not always protective: excessive matrix stiffness can itself promote cancer-related phenotypes. An open question is whether maintaining or restoring the normal range of mechanical tension within tissues makes malignant transformation less likely. Evidence linking measures of tensional homeostasis to subsequent transformation, or experiments showing that restoring normal mechanical balance changes the probability of transformation, could distinguish whether disrupted tissue mechanics merely accompanies cancer or can contribute causally to its initiation.