Snail1-driven plasticity of epithelial and mesenchymal cells sustains cancer malignancy

Abstract

The transcription factor Snail1 induces epithelial-to-mesenchymal transition (EMT) in tumor epithelial cells, a process associated with the emergence of stemness, invasion and cancer malignancy. Here, we review recent reports indicating that Snail1 also regulates mesenchymal plasticity and paracrine signaling and propose that Snail1 orchestrates the generation of cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs). Our view supports the current models for tumorigenesis that consider stemness and tumor microenvironment as retroactive actors for metastasis formation, revealing Snail1 as a regulator of these metastatic forces. This view offers new perspectives for understanding and targeting metastasis.

Keywords: CAF Cancer associated fibroblasts; CSC Cancer stem cell; EMT Epithelial to mesenchymal transition; Mechanical signalling; Metastasis; Snail1; TGF-beta; Tumor microenvironment.