Snail2: roles and regulatory mechanisms in development and disease

Abstract Snail2 (SNAI2/Slug), a core C2H2 zinc-finger transcription factor of the Snail superfamily, functions as a master regulator of epithelial-mesenchymal transition (EMT) and cellular plasticity in development and disease. Unlike other EMT transcription factors that drive complete transition, Snail2 distinctively promotes partial EMT—a reversible hybrid epithelial/mesenchymal state essential for tumor dissemination and metastatic seeding. Snail2 expression and activity are governed by a multi-layered network spanning transcriptional, post-transcriptional, translational, and post-translational control. During developmental processes, Snail2 is critical for neural crest formation and migration, while also orchestrating gland development, vascular development, cardiac valve development, chondrogenesis and skeletal development. In pathological contexts, Snail2 drives cancer progression through epigenetic reprogramming of epithelial and mesenchymal genes, conferring invasion, metastasis, stemness, and chemoresistance; it is also implicated in cardiovascular, respiratory, renal, and gynecological disorders through EMT-mediated tissue remodeling and inflammation. Critical gaps remain in understanding the molecular determinants of partial EMT, context-dependent functional diversity, translational control mechanisms, and Snail2’s emerging role in tumor immune microenvironment. Elucidating these mechanisms will advance fundamental understanding of developmental and cancer biology and inform therapeutic strategies targeting metastatic disease.