Contribution of mechanical homeostasis to epithelial-mesenchymal transition

Metastasis refers to the spread of cancer cells from a primary tumor to other parts of the body via the lymphatic system and bloodstream. With tremendous effort over the past decades, remarkable progress has been made in understanding the molecular and cellular basis of metastatic processes. Metastasis occurs through five steps, including infiltration and migration, intravasation, survival, extravasation, and colonization. Various molecular and cellular factors involved in the metastatic process have been identified, such as epigenetic factors of the extracellular matrix (ECM), cell-cell interactions, soluble signaling, adhesion molecules, and mechanical stimuli. However, the underlying cause of cancer metastasis has not been elucidated.

In this review, we have focused on changes in the mechanical properties of cancer cells and their surrounding environment to understand the causes of cancer metastasis. Cancer cells have unique mechanical properties that distinguish them from healthy cells. ECM stiffness is involved in cancer cell growth, particularly in promoting the epithelial-mesenchymal transition (EMT). During tumorigenesis, the mechanical properties of cancer cells change in the direction opposite to their environment, resulting in a mechanical stress imbalance between the intracellular and extracellular domains. Disruption of mechanical homeostasis may be one of the causes of EMT that triggers the metastasis of cancer cells.