Molecular mechanisms of epithelial to mesenchymal transition in tumor metastasis

Abstract

Epithelial to mesenchymal transition (EMT) is a process where cancer cells lose their epithelial features, the cy- toskeletal architecture is re-organized, the cell shape changes and cells activate genes that help to define a mesenchymal phenotype, which leads to an increased cell motility and dissemination of tumor to distant meta- static sites. This review describes different signaling networks between microRNAs and proteins that regulate EMT in tumor growth. Activation of EMT is mediated via a series of paracrine signaling molecules. WNT, TGF-P, NOTCH and SHH signaling pathways play crucial roles in activation of EMT-related transcription factors, such as SNAIL, SLUG, ZEB1/2 or TWIST. Recent data provide evidence that crosstalk between microRNAs, long non- coding RNAs and EMT-transcription factors is a crucial event in EMT regulation. MicroRNAs also affect the level of proteins responsible for cellular contact, adhesion and cytoskeletal proteins, which induces changes in the epithelial to mesenchymal phenotype transition. Understanding those signaling networks may help to identify novel biomarkers or develop new treatment strategies based on microRNA therapeutics in the future.