“Say Yes to the Stress”: the perfectly tailored mechanical environment for tumor metastasis

Abstract

The main cause of cancer lethality is metastasis. Throughout cancer progression cells are affected by mechanical forces. Forces like tension, compression and shear of fluid flow can be generated and sensed by cells (mechanosensing), and can biochemically be transduced (mechanotransduction), leading to alterations in cellular fate and behavior. In tumors, changes can occur in how cells sense forces in the environment, or the environment can change. Tumor cells are affected by changes in extracellular matrix (ECM) composition and mechanical strength, of which these changes can also be induced by the tumor itself or tumor-recruited stromal cells. Mechanical forces and sensing of them are involved in many steps of metastasis, from the local environment of the primary tumor, to dissemination through circulation, re-entry into tissues and colonization of secondary sites. In this review we discuss our current understanding of the contribution of mechanosensing and mechanotransduction at several steps of the metastatic cascade, including mechanical changes prior to colonization caused by cancer, various pathologies and aging.