In a recent study, Guo et al. showed that sphingosine-1-phosphate receptor 2 upregulated nuclear TWIST1 (twist family bHLH transcription factor 1) through activation of the Hippo/TEAD1-TWIST1 pathway, and that nuclear TWIST1 interacted with the KDM6B-RNA Pol II complex, leading to dihydropyrimidine dehydrogenase transcription through H3K27me3 demethylation, which mediated 5-fluorouracil resistance in CRC [169]. The gene discussed is TEAD1; the disease is colorectal carcinoma.