Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane Hidaka, Saitama, 350-1241, Japan.
Division of Radioisotope, Saitama Medical University, 1397-1 Yamane Hidaka, Saitama, 350-1241, Japan.
Sci Rep. 2019 Jul 29;9(1):10933. doi: 10.1038/s41598-019-47301-6.
YAP (also known as YAP1 or YAP65) is a transcriptional coactivator that interacts with a number of transcription factors including RUNX and TEAD and plays a pivotal role in controlling cell growth. YAP is classified as a proto-oncogene. However, the mechanism by which activated YAP induces cancerous changes is not well known. Here we demonstrate that overexpression of YAP in NIH3T3 cells was sufficient for inducing tumorigenic transformation of cells. Mechanistically, YAP exerts its function in cooperation with the TEAD transcription factor. Our data also show that cMYC is a critical factor that acts downstream of the YAP/TEAD complex. Furthermore, we also found that aberrant activation of YAP is sufficient to drive tumorigenic transformation of non-immortalized mouse embryonic fibroblasts. Together our data indicate that YAP can be categorized as a new type of proto-oncogene distinct from typical oncogenes, such as H-RAS, whose expression in non-immortalized cells is tightly linked to senescence.
YAP（也称为 YAP1 或 YAP65）是一种转录共激活因子，与包括 RUNX 和 TEAD 在内的许多转录因子相互作用，在控制细胞生长方面发挥着关键作用。YAP 被归类为原癌基因。然而，激活的 YAP 诱导癌变的机制尚不清楚。在这里，我们证明 YAP 在 NIH3T3 细胞中的过表达足以诱导细胞发生肿瘤转化。从机制上讲，YAP 通过与 TEAD 转录因子合作发挥其功能。我们的数据还表明，cMYC 是一个关键因素，它作为 YAP/TEAD 复合物的下游发挥作用。此外，我们还发现 YAP 的异常激活足以驱动非永生化小鼠胚胎成纤维细胞的肿瘤转化。总之，我们的数据表明，YAP 可以被归类为一种不同于典型致癌基因（如 H-RAS）的新型原癌基因，其在非永生化细胞中的表达与衰老密切相关。
