Fig. 5: Benzamide family HDAC inhibitors induce YAP transcription via the SIN3A-HDAC complex.
From: YAP silencing by RB1 mutation is essential for small-cell lung cancer metastasis
a Entinostat induces YAP and CCN2 expression. H209 and H69 cells were treated with 1 µM entinostat, 0.3 µM TSA, 1 µM GSK-LSD1, 1 µM DZNep, and 10 µM decitabine for 24 hours. b 1 µM entinostat treatment for 24 hours induces YAP protein in H209 and H69 cells. c TSA prevents entinostat from inducing YAP expression in H209 and H69 cells. d SIN3A/B KO prevents entinostat from inducing YAP expression in H209 and H69 cells. e TSA treatment blocks YAP induction by RCOR1/2/3 KO in H209 and H69 cells. f SIN3A/B KO suppresses YAP mRNA and protein induction by RCOR1/2/3 KO in H209 and H69 cells. g A proposed mechanism of YAP transcription regulation. RB1 acts through the E2F7-RCOR axis, while SIN3A/B is required for YAP expression in SCLC. h KO of SIN3A/B but not RCOR1/2/3 blocks YAP induction by RB1 re-expression in H209 and H69 cells. i SIN3A/B KO but not RCOR1/2/3 KO blocks YAP induction by E2F7/8 KO in H209 and H69 cells. j TSA suppresses RB1 rescue-induced YAP expression in H209 and H69 cells. k TSA suppresses E2F7/8 KO-induced YAP expression in H209 and H69 cells. l Entinostat but not TSA increases SIN3A occupancy on the YAP promoter. m E2F7 expression blocks RB1-induced SIN3A occupancy on the YAP promoter. n Benzamide HDAC inhibitors induce YAP protein in H209 and H69 cells. Source data are provided as a Source data file.
