Ezrin regulates the progression of NSCLC by YAP and PD-L1

Purpose: To determine whether ezrin regulates Yes-associated protein (YAP) and programed cell death ligand-1 (PD-L1), which are involved in the invasion and metastasis of non-small cell lung cancer (NSCLC).

Methods: Immunohistochemistry of 164 NSCLC and 16 para-cancer tissues was performed to detect ezrin, YAP, and PD-L1 expression. Further, H1299 and A549 cells were transfected with lentivirus, and then colony formation, CCK8, transwell, and wound-healing assays were used to assess cell proliferation, migration, and invasion. RT-qPCR and western blotting were used for quantitative analysis of ezrin, PD-L1, and YAP expression. Moreover, the role of ezrin in tumor growth was assessed in vivo, and immunohistochemistry and western blotting were performed to evaluate changes in ezrin expression in mouse samples.

Results: The positive protein expression rates of these molecules in NSCLC were as follows: ezrin, 43.9% (72/164); YAP, 54.3% (89/164); and PD-L1, 47.6% (78/164); these were higher than those in normal lung tissues. Moreover, YAP and ezrin expression positively correlated with PD-L1 expression. Ezrin promoted proliferation, migration, invasion, and expression of YAP and PD-L1in NSCLC. Inhibition of ezrin expression reduced the effects of ezrin on cell proliferation, migration, invasion, inhibited the expression of YAP and PD-L1, and obviously reduced experimental tumor volume in vivo.

Conclusions: Ezrin is overexpressed in NSCLC patients and correlates with PD-L1 and YAP expression. Ezrin regulates YAP and PD-L1 expression. Inhibition of ezrin delayed NSCLC progression.