Fig 2: CBX2 knockdown promotes YAP phosphorylation, and its nuclear and cytoplasm translocation. The expression of total and P-YAP was determined in gastric cancer cells transfected with shRNA-CBX2 via western blotting. Data are presented as the mean ± SEM from three independent experiments. ***P<0.001 vs. Control. CBX2, chromobox homolog 2; YAP, yes-associated protein; shRNA, short hairpin RNA; P, phosphorylated; NC, negative control.

Fig 3: Small cell lung cancer (SCLC) molecular subtypes identification by the non-negative matrix factorization (NMF) algorithm.A The protein expression levels of achaete-scute homologue 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), yes-associated protein 1 (YAP1), and POU class 2 homeobox 3 (POU2F3) in SCLC tumors. B Cophenetic correlation from NMF analysis of 100 SCLC samples. C NMF consensus matrix of 4 SCLC molecular subtypes. D The proportion of 4 SCLC molecular subtypes in the primary cohort. E The expression levels of ASCL1, NEUROD1, POU2F3, and YAP1 among 4 SCLC subtypes. ns, not significant; *p < 0.05.

Fig 4: YAP1 regulated PD-L1 expression in small cell lung cancer (SCLC).A mRNA expression level of PD-L1 in different SCLC cell lines. B, C MFI of PD-L1 in different SCCL cell lines. D, F Microscopy of SHP77, H446, and H526 cell lines with stable overexpression of YAP1. Histograms depicted MFI of nuclear-localized YAP1 in SCLC-OE and NC cells. G Gating strategy of SCLC cells with stable overexpression of YAP1. H MFI of PD-L1 in OE and NC cells. I MFI of nuclear-localized YAP1 and PD-L1 in SCLC-Y cells after verteporfin exposure. MFI median fluorescence intensity, NC negative control, OE overexpression, PD-L1 program death-ligand 1, YAP1 yes-associated protein 1.

Fig 5: The molecular basis of YAP1 inhibitor in combination with immunotherapy in SCLC.High YAP1 expression induces PD-L1 expression, thus leading to the inhibition of T cells infiltration and function. The combinational treatment of YAP1 inhibitor and ICI significantly promotes apoptosis of tumor cells and activation of T cells. The addition of YAP1 inhibitor further enhances anti-tumor immunity. ICI immune checkpoint inhibitor, PD-1 program death-1, PD-L1 program death-ligand 1, SCLC small cell lung cancer, Treg regulatory T cells, YAP1 yes-associated protein 1.