The role of YAP1 in small cell lung cancer

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also known as WWTR1) are core downstream effectors of the Hippo pathway, which is involved in diverse biological processes. The oncogenic effects of YAP and TAZ in non-small cell lung cancer (NSCLC) have recently been reported; however, their roles in SCLC remain unclear. Immunohistochemistry (IHC) on lung cancer tissues and Western blotting (WB) on lung cancer cell lines were performed to examine the expression of YAP1. Genome editing using CRISPR/Cas9 was then used to knockout the YAP1 gene in the H69AR cell line. An RNA-sequence analysis, gene ontology (GO) analysis, WB, cell counting assay, invasion assays, and xenograft studies were conducted on these cells to investigate the biological roles of YAP1. IHC revealed that insulinoma-associated protein 1 was expressed in most cases (28 out of 32 cases), while only four cases expressed YAP1. The knockout of YAP1 in H69AR cells, a chemically induced SCLC-Y subtype, reduced cell proliferation and invasion capacity and restored drug sensitivity. Xenograft assays revealed that the knockout of YAP1 suppressed cell proliferation. Tumor tissues showed the expression of neuroendocrine markers and a low Ki-67 index. In SCLC, YAP1 plays an important role in biological functions, such as cell proliferation, EMT, drug sensitivity, and neuroendocrine differentiation.