HIF as a modulator of EMT. Simplified overview of hypoxia/HIF-regulated EMT-triggering signaling pathways and effector molecules. The composition and integrity of the basement membrane is crucial for the maintenance of epithelial homeostasis, and its disruption is a critical event during the EMT process. Under pathological conditions, transitioned epithelial cells migrate into the interstitium, where they produce ECM as myofibroblasts. Migration is likely to be modulated by HIF via increased expression of proteins that regulate and balance ECM degradation and turnover, such as PAI1 and TIMP1. Abbreviations: CTGF, connective tissue growth factor; PAI1, plasminogen activator inhibitor 1; TIMP1, tissue-inhibitor of metalloproteinase 1; RTyrKinases, receptor tyrosine kinases; SNAI1, snail homologue 1; TCF3, transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47); ZEB, zinc finger E-box-binding homeobox.