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. 2022 Aug 8;7(15):e159930. doi: 10.1172/jci.insight.159930

Figure 2. SHP2 inhibition activates YAP/TAZ in vitro and in vivo.

Figure 2

(A) Hu1545 whole cell lysates treated with vehicle, NSC (1 μM for 24 hours), or SHP099 (1 μM for 24 hours) probed for pYAPY357, pYAPS127, total YAP, and actin as a loading control. (B) Representative image of YAP and TAZ immunofluorescence stains in Hu1545 treated with vehicle, NSC (1 μM), or SHP099 (1 μM). Inset image with DAPI overlay. Scale bar: 50 μm for both inset and main image. YAP and TAZ mean fluorescence intensity (MFI) from 75 to 100 nuclei/condition plotted as a violin plot (solid line, median; dashed line, upper or lower quartile). (C) Hu1545 YAP/TAZ target gene expression (CTGF, NUAK2, and CYR61) following treatment with vehicle, NSC (1 μM for 24 hours), and NSC with 6- or 24-hour washout (n = 3–4). Data are shown as mean ± SEM. (D) Hu1545 YAP/TAZ target gene expression in vehicle- or SHP099-treated cells (1 μM for 24 hours) (n = 3). (E) YAP/TAZ target genes Ctgf and Nuak2 from livers treated with vehicle or NSC at baseline (resection specimen), 40, and 72 hours after hepatectomy (n = 3). (F) Mean liver/body weight ratio 72 hours after hepatectomy in Yapfl/fl/Tazfl/fl and YapΔhep/TazΔhep mice treated with vehicle or NSC (n = 4). Data are shown as mean ± SEM unless otherwise specified (*P < 0.05, **P < 0.01, ***P < 0.001). Statistical analysis was performed with 1-way ANOVA (B, C, E, and F) and 2-tailed Student t test (C).