SOX2 and cancer: Binding motifs for many essential TFs, such as RXRA, NFE2L2, ESRRA, IRF2, RELA, ESRRA, SOX2, and SMAD2/3 (Fig. 4a, b), key TFs that mediate TGFβ signaling in epithelial-mesenchymal transition (EMT) and cancer metastasis11,40, were enriched in common gained or LNC-specific gained enhancers, with some overlapping TFs.