Mechanotransduction pathways in regulating epithelial-mesenchymal plasticity.

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.

Regulation of epithelial-mesenchymal transition by tumor microenvironmental signals and its implication in cancer therapeutics.

Epithelial-mesenchymal transition (EMT) has been implicated in various aspects of tumor development, including tumor invasion and metastasis, cancer stemness, and therapy resistance. Diverse stroma cell types along with biochemical and biophysical factors in the tumor microenvironment impinge on the EMT program to impact tumor progression. Here we provide an in-depth review of various tumor microenvironmental signals that regulate EMT in cancer. We discuss the molecular mechanisms underlying the role of EMT in therapy resistance and highlight new therapeutic approaches targeting the tumor microenvironment to impact EMT and tumor progression.