Hypoxia-inducible factor (HIF-1α) has been shown to synergize with CAFs paracrine signals, namely TGF-β2, to activate hedgehog transcription factor GLI2 in cancer stem cells (CSCs), leading to enhanced stemness/dedifferentiation and intrinsic resistance to chemotherapy of colorectal cancer (Tang et al., 2018). The gene discussed is HIF1A; the disease is colorectal cancer.