Yes-Associated Protein Upregulates Jagged-1 and Activates the NOTCH Pathway in Human Hepatocellular Carcinoma

Darjus Felix Tschaharganeh; Xin Chen; Philipp Latzko; Mona Malz; Matthias Martin Gaida; Klaus Felix; Sara Ladu; Stephan Singer; Federico Pinna; Norbert Gretz; Carsten Sticht; Maria Lauda Tomasi; Salvatore Delogu; Matthias Evert; Biao Fan; Silvia Ribback; Lijie Jiang; Stefania Brozzetti; Frank Bergmann; Frank Dombrowski; Peter Schirmacher; Diego Francesco Calvisi; Kai Breuhahn

doi:10.1053/j.gastro.2013.02.009

Figure 7

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Concomitant activation of YAP/Jag-1 in pancreatic and colon cancer specimens

(A) Association between YAP and Jag-1 and between YAP and Hes-1 transcript levels in 11 human PDACs. (B) Representative H/E staining and immunohistochemical analysis for YAP and Jag-1 in pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) specimens. Original magnification: ×200. (C) Western blot analysis of YAP, Jag-1, and NICD in Panc-1 cells after siRNA-mediated silencing of YAP. Untreated (cont.) and scramble siRNA-transfected cells served as controls. Hes-1 transcript levels were determined by real-time PCR. (D) Viability kinetics of Panc-1 cells after inhibition of YAP measured by MTT-assay 48, 72, and 96 h after siRNA transfection for YAP (left) and Jag-1 (right). Untreated (cont.) and scramble-transfected cells served as controls. Values represent means ± SD. Statistical test: Mann-Whitney U; n.s. - not significant, **p<0.01. (E) Association between YAP and Jag-1 as well as between YAP and Hes-1 transcript levels in 40 human CRC samples. (F) Representative Western blots from human CRC tissue samples (n=40) and respective surrounding colon tissue (SC; n=40). Jag-1, NICD, total YAP, nuclear YAP (after fractionation), TEAD4, and Hes-1 were detected. Actin and histone H3 were used as loading controls for total protein and nuclear protein fractions, respectively. For (A) and (E) the Spearman rank coefficient was used as a statistical measure of association.