Mechanotransduction pathways in regulating epithelial-mesenchymal plasticity

Abstract

The extracellular matrix (ECM) provides structural support for cells and mediates cell-stromal communications. In addition to ECM proteins, mechanical force exerted from the ECM serves as a critical regulator of many biological processes. Epithelial-mesenchymal transition (EMT) is a cellular process by which epithelial cells loosen their cellular junctions and migrate and invade in a more mesenchymal fashion. Recent studies show that increasing ECM stiffness can impinge on cellular signaling pathways through mechanotransduction to promote carcinoma cells to undergo EMT, suggesting that mechanical force exerted by the ECM plays a critical role in tumor invasion and metastasis. Here, we highlight recent work utilizing innovative approaches to study mechanotransduction and summarize newly discovered mechanisms by which mechanosensors and responders regulate EMT during tumor progression and metastasis.

Figure 1.

A schematic of various physical forces tumor cells experience during the metastatic cascade. The mechanical forces are labeled, and the upstream factors contributing to the mechanical force are depicted at both the site of primary tumor growth and in the blood circulation.

Figure 2.

A schematic of the signaling pathways by which YAP/TAZ function as mechano-responders to induce EMT at high matrix stiffness in various human cancers.