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. 2024 Apr 24;7:497. doi: 10.1038/s42003-024-06190-w

Fig. 3. The Hippo pathway modulates osimertinib response in EGFR mutant lung cancer.

Fig. 3

Isogenic cell lines PC-9, HCC827, and HCC4006 were used to determine the effect of NF2 knockout on: a osimertinib resistance in 21-day clonogenic survival assays, b key EGFR signaling pathway post osimertinib treatment (24 hours) by western blot, c, d nuclear YAP1/WWTR1 expression (Wilcoxon rank sum test, ***p < 0.001) and activation of a TEAD reporter system (Student’s t-test, **p < 0.01, ***p < 0.001). The right panel of (C) shows representative IF images of YAP1/WWTR1 fluorescence in NF2 KO vs NTC cells. e Effect on viability over 15 days in NF2 KO PC-9 cells when YAP1, WWTR1, or YAP1/WWTR1 were silenced and cells treated with DMSO vs osimertinib. f Effect in PC-9 cells of doxycycline-dependent expression of wild-type or mutant YAP1 or WWTR1 on viability following osimertinib treatment over 21 days. g Dose dependency effect of doxycycline on osimertinib resistance at 21 days in PC-9 cells for wild-type and mutant forms of YAP1 and WWTR1.