Extended Data Fig. 10: Loss of LATS2 is enriched in the TRACERx LUSC cohort.
a, Representative western blot following LATS1/2 knockdown in the U2OS-AsiSI DIvA system reveals that DNA damage markers such as γH2A.X and phospho-KAP1 are activated proficiently upon damage. b, Middle, representative gel showing that transient knockdown of LATS2, but not LATS1, induces an illegitimate repair product in U2OS-AsiSI DIvA cells. PCR products generated from the legitimate repair product were used as the loading control (bottom). n=3 biological repeats. c, Plots of GISTIC scores illustrating that the SCNA loss of the LATS2 genomic loci (13q12.11) is positively selected in the LUSC but not the LUAD TRACERx421 cohort. Red lines denote q value <0.2. d,e, Histograms representing cell cycle profiles following loss of FAT1, YAP1 or combined loss of both FAT1 and YAP1 by siRNA in U2OS-AsiSI cells (d) and A549 FAT1 WT/KO cells (e), n=3 biological repeats, one-way ANOVA with Sidak corrections. f, Histogram quantifying the percentage of FAT1 WT or KO A549 cells with lagging chromosomes after aphidicolin treatment following transient depletion of YAP1 using RNAi, mean±SD, one-way ANOVA with Holm-Sidak multiple correction, biological repeats: FAT1 WT =3, FAT1 KO =4. g, Representative western blot showing YAP1 and FAT1 knockdown efficiency in the RPE1-FUCCI and A549 cells. h, Proposed model showing potential interaction between FAT1 and the Hippo pathway.
