Supplementary Figure S3 from MARK2/MARK3 Kinases Are Catalytic Codependencies of YAP/TAZ in Human Cancer

Le résumé fourni par la source

A, Mutational two-class comparison between 19 MARK2/3-dependent and 12 MARK2/3-independent human cancer cell lines (shown in B). Mutation data were obtained from the CCLE database. The effect size and P values were calculated for every mutated gene of the cell lines using a linear association model. B, C, Competition-based fitness assays in Cas9-expressing cancer cells after lentiviral knockout of indicated genes (expression of double guide RNAs (dgRNA) was linked to GFP). Heatmap color indicates the log2(fold-change) of normalized GFP (%GFP+ normalized to day 3 or 6 after infection). n=3. D, E, Western blot analysis in Cas9+ YAPC cells. F, Crystal violet stain of YAPC and CHL-1 (MARK2/3 independent) cells following dgRNA assisted lentiviral knockout of indicated genes. Data are representative of three independent experiments. G, CUT&RUN density profile of YAP/TAZ sensitive H3K27ac marked enhancer loci (n=7,896) following YAP+TAZdKO. Profiles shown are an average of 50bp bins around the summit of the enhancers. H, I, Occupancy profiles of public Chromatin immunoprecipitation sequencing (ChIP-seq) (TEAD4, YAP) (GSE66083) and CUT &RUN (H3K27ac) upon indicated gene knockout at YAP/TAZ target gene loci. (Three different dgRNAs for MARK2+3) (Data shown are an extension of Fig. 2I).

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.