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. Author manuscript; available in PMC: 2017 Apr 6.
Published in final edited form as: Nature. 2016 Sep 28;538(7623):114–117. doi: 10.1038/nature19771

Figure 4. Concurrent mutations in FSTL5 are associated with intrinsic resistance of KRAS-mutant lines to XPO1 inhibitors and are mechanistically coupled to YAP1 activation.

Figure 4

a, Biclustering results for NSCLC cell lines and KRAS and FSTL5 mutation status. b, Selective effects of FSTL5 depletion on the XPO1-inhibitor-sensitivity of KRAS-mutant, FSTL5-wild-type lines (red) versus KRAS-mutant, FSTL5-mutant lines (green). Box plot indicates fold changes in area under the curve (AUC) of FSTL5 siRNA (siFSTL5)-transfected cells normalized to negative control siRNA-transfected cells. AUCs calculated from Extended Data Fig. 5f, g. Unpaired t-test, P = 0.0411. c, Significant enrichment of YAP1 protein in tumours harbouring FSTL5 somatic alterations (data taken from the TCGA-LUAD). Unpaired t-test, P = 0.0149. d, YAP1 protein accumulation 72 h post-transfection with FSTL5 siRNAs. e, YAP1 immunohistochemistry. Detected somatic FSTL5 variants are indicated. Representative YAP1 immunohistochemistry stains are shown in the right panel. f, Induction of XPO1-inhibitor resistance by YAP1 overexpression (crystal-violet stained). g, Induction of XPO1 inhibitors sensitivity by verteporfin/AICAR-mediated YAP pathway inhibition (crystal-violet stained).