EMT signaling: potential contribution of CRISPR/Cas gene editing

Abstract

Epithelial to mesenchymal transition (EMT) is a complex plastic and reversible cellular process that has critical roles in diverse physiological and pathological phenomena. EMT is involved in embryonic development, organogenesis and tissue repair, as well as in fibrosis, cancer metastasis and drug resistance. In recent years, the ability to edit the genome using the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system has greatly contributed to identify or validate critical genes in pathway signaling. This review delineates the complex EMT networks and discusses recent studies that have used CRISPR/Cas technology to further advance our understanding of the EMT process.

Keywords: CRISPR; Cancer; Epithelial–mesenchymal transition; Gene editing.

Fig. 1

Distinct intermediate states of epithelial–mesenchymal transition in the progression of carcinoma. EMT is a functional transition of differentiated epithelial cells into migratory mesenchymal cells. A list of EMT-inducers and common markers expressed in the epithelial and mesenchymal cells during EMT and its reversal process MET are provided. Colocalization and combinatorial expression of these distinct markers define intermediate EMT phenotypes. EMT enables the transitioned mesenchymal-like carcinoma cells to reduce or lose intracellular adhesion and gain invasive potential. This allows them to intravasate into the blood and lymph vessels and subsequently extravasates to form micrometastases, which can revert to an epithelial-like state through MET and thus forming a clinically detectable tumor

Fig. 2

CRISPR toolkit is applied to study EMT. Different approaches including gene knockout, knockdown, knock-in, and epigenetic regulation are achieved by the CRISPR/Cas technology to study EMT-related genes and pathways and identify novel drugs to control the EMT process