Fig. 2: MGH-CP1 treatment overlaps with YAP/TAZ suppression in transcriptional output and inhibits YAP-dependent transformation, organ enlargement, and tumor initiation.
From: Pharmacological blockade of TEAD–YAP reveals its therapeutic limitation in cancer cells
a Fisher’s Exact Test using RNA-seq datasets of MGH-CP1 (GSE177052) versus YAP/TAZ knockdown (GSE102407) in MDA-MB-231 cells. Two tailed P values are shown. b Gene set enrichment analysis of YAP/TAZ-TEAD target gene signature upon MGH-CP1 treatment. c Tumor sphere formation assay of MCF10A cells transduced with YAP WT or S127A mutation. Indicated doses of MGH-CP1 were applied. Tumor sphere numbers were counted in d (n = 4 biological repeats). Scale bar, 100 µm. e MGH-CP1 inhibits liver enlargement induced by liver specific Lats1/Lats2 deletion in vivo. Scale bar, 1 cm. f Quantification of relative liver weight of control or MGH-CP1-treated Lats1fl/fl;Last2fl/fl mice with control or Lentiviral-Cre delivery (n = 4 mice). g Representative images of histology and IHC of YAP/TAZ and phospho-histone H3 (p-H3) in the liver. Scale bar, 50 µm. (Images were chosen from n = 9, 6, 5 histology fields for Control, Lats1/Lats2 double knockout and Lats1/Lats2 double knockout with MGH-CP1, respectively) h Percentage of phospho-histone H3 positive cells in the liver of control and Lats1/Lats2 double knockout mice treated with MGH-CP1 (n = 9, 6, 5 histology fields for Control, Lats1/Lats2 double knockout and Lats1/Lats2 double knockout with MGH-CP1, respectively). i Xenograft tumor volumes of Huh7 cells inoculated in SCID mice, and then treated with vehicle control or MGH-CP1 (n = 9, 10 tumors for control and MGH-CP1, respectively). j Relative mRNA levels of CTGF and Cyr61 were determined using qPCR in xenograft tumors. All the mRNA levels were normalized to 18S rRNA (n = 9, 10 tumors for control and MGH-CP1, respectively). k The image of xenograft tumors are shown for tumor initiation. Tumor volumes were determined (n = 10 tumors). l The images of xenograft tumors pre-treated with Control or MGH-CP1 (10 µM for 24 h) ex vivo, before inoculation into animals. Tumor weights were measured (n = 5 tumors). Data are represented as mean ± S.E.M. P values were determined using two-tailed t-tests. Source data are provided as a Source Data file.
