ZEB1 and neoplasm: In addition to its role in metabolism, HIF-1 contributes to GBM invasiveness by promoting EMT through the activation of the Snail and ZEB1 transcription factors, downregulating E-cadherin, and enhancing ECM remodeling.226 HIF-1 also upregulates matrix MMPs (MMP-2, MMP-9, and MMP-14), cathepsins, and fibronectin, facilitating basement membrane degradation and tumor cell migration.227 Furthermore, it fosters an immunosuppressive microenvironment by increasing lactate production and adenosine accumulation, which suppress T cell function and enhance regulatory T cell (Treg) activity.