Transformation of normal cells by aberrant activation of YAP via cMyc with TEAD
Transformation of normal cells by aberrant activation of YAP via cMyc with TEAD
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DOI：
10.1038/s41598-019-47301-6
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发表时间：
2019-07
影响因子：
4.6
通讯作者：
M. Nishimoto;Kousuke Uranishi;Masamitsu N. Asaka;Ayumu Suzuki;Y. Mizuno;Masataka Hirasaki;A. Okuda
中科院分区：
文献类型：
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作者：
M. Nishimoto;Kousuke Uranishi;Masamitsu N. Asaka;Ayumu Suzuki;Y. Mizuno;Masataka Hirasaki;A. Okuda
雅普（也称为YAP 1或YAP 65）是一种转录辅激活因子，其与包括RUNX和TEAD在内的许多转录因子相互作用，并且在控制细胞生长中起关键作用。然而，激活的雅普诱导癌变的机制尚不清楚。在这里，我们证明了雅普在NIH 3 T3细胞中的过表达足以诱导细胞的致瘤性转化。在机制上，雅普与TEAD转录因子合作发挥其功能。我们的数据还表明cMYC是作用于雅普/TEAD复合物下游的关键因子。此外，我们还发现雅普的异常激活足以驱动非永生化小鼠胚胎成纤维细胞的致瘤转化。总之，我们的数据表明，雅普可以被归类为一种新型的原癌基因，不同于典型的癌基因，如H-RAS，其表达在非永生化细胞中与衰老密切相关。
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.YAPis 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 asH-RAS, whose expression in non-immortalized cells is tightly linked to senescence.