Fig. 4

EMT transcriptionally induces STT3 through β-catenin/TCF4. a ENCODE data display ChIP-seq signals for the occupancy of TCF4 (TCF7L2), histone H3K4Me3, and DNase Clusters around the transcription start sites of STT3A and STT3B. H3K4Me3 and DNase Clusters were used to define the transcriptional regulatory regions of STT3A and STT3B. These ENCODE data were generated by the ENCODE consortium and available on the Genome Browser at UCSC. b Pearson correlation analysis of β-catenin (CTNNB1) with STT3A and STT3B in TCGA breast cancer dataset (n = 1100). c Top: schematic presentation of the wild-type (wt) and TCF4-binding-site-mutated (mt) STT3 promoter-luciferase reporter constructs of STT3A (−1042/+210, related to the transcription start site) and STT3B (−1381/−1, related to the transcription start site). The TCF4 binding sites on the promoter regions of STT3A (⁻²⁸² GCAAACCGACA⁻²⁷²) or STT3B ⁽⁻⁸⁸⁹TCACGTGGTGA⁻⁸⁷⁹, ⁻⁶⁷¹TCTTTCAACTG⁻⁶⁶¹) are shown. Bottom: promoter luciferase activity in response to β-catenin (β-Cat) and TCF4 dominant-negative (TCF4-DN) mutant. d Effect of β-catenin (β-Cat) and TCF4-DN on the protein and mRNA expression of STT3 isoforms in MCF-10A cells. e Influence of STT3 knockdown on β-catenin (β-Cat)-mediated PD-L1 induction in MCF-10A cells; s.e. short exposure, l.e. long exposure. f Effect of β-catenin knockdown (si-β-Cat) and TCF4-DN on TGF-β-mediated PD-L1 induction in MCF-10A cells. g Effect of β-catenin knockdown (si-β-Cat) on the expression of STTA/B and PD-L1 in mesenchymal-like BT-549 cells. Error bars represent s.d. (n = 3). *P < 0.05, Student’s t-test