Before metastasis, the niche needs to undergo mesenchymal epithelial transformation to promote the infiltration and colonization of tumor cells.150,151 Numerous cytokines and signaling pathways, such as TGF-β, Wnt, Notch, and Hedgehog, are involved in regulating EMT.152,153 Tumor-derived exosomes can carry TGF-β, hypoxia-inducible factor 1α (HIF1α) and β-catenin, which are factors that promote EMT.154,155. This evidence concerns the gene HIF1A and neoplasm.