Epithelial-Mesenchymal Transition in Cancer

Abstract

Epithelial-mesenchymal transition (EMT) is a reversible process that enables carcinoma cells to become invasive and therapy-resistant, thereby affecting clinical outcomes such as relapse and treatment failure. In tumors, EMT is triggered by pathways such as TGF-β, Wnt/β-catenin, Notch, PI3K/Akt/mTOR, MAPK, hypoxia, and inflammatory cytokines. These activate EMT-inducing transcription factors, including Snail, Slug, Twist, and ZEB1/2. Noncoding RNAs, like the ZEB–miR-200 axis, also play roles. These changes create intermediate epithelial–mesenchymal states linked to collective migration, stemness, tumor recurrence, and therapy resistance. EMT also promotes immune evasion. Myeloid and stromal cells, especially tumor-associated macrophages and MDSCs, promote EMT and suppress antitumor immunity. EMT reduces antigen presentation, increases immune checkpoints such as PD-L1, and alters chemokines to attract immunosuppressive T cells, helping tumors evade detection. EMT contributes to multidrug resistance by altering cell adhesion and motility and by activating kinases such as STAT3, AXL, and EGFR/ERK. Targeting or reversing EMT can increase tumor sensitivity to treatment and improve outcomes. Combinations of EMT inhibitors (e.g., TGF-β and PI3K inhibitors), epigenetic therapies, and RNA-based reprogramming are being evaluated. New multi-omics and liquid biopsy technologies enable real-time monitoring of EMT status to support more personalized care. Recognizing EMT as a key driver of tumor progression creates new opportunities for targeted treatment.