Verteporfin induced SUMOylation of YAP1 in endometrial cancer.
Verteporfin induced SUMOylation of YAP1 in endometrial cancer.
复制标题
维替泊芬诱导子宫内膜癌中 YAP1 的 SUMO 化。
DOI：
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发表时间：
2020-04
影响因子：
5.3
通讯作者：
Chao Wang
中科院分区：
文献类型：
--
作者：
Bo Wang;Wenyu Shao;Yue Shi;Jiongbo Liao;Xiaojun Chen;Chao Wang
Yes相关蛋白（雅普或YAP 1）已被认为是大多数癌症中的癌基因，YAP 1的核定位与不良预后相关。光敏剂Verteporfin通过阻止YAP 1与TEA结构域转录因子（TEAD）的结合而被证明是YAP 1的抑制剂。我们以前表明，总的和磷酸化水平的YAP 1相关的临床特征和结果在子宫内膜癌（EC）患者，和YAP 1促进EC细胞的增殖和转移的体外细胞系研究和动物模型。我们在前期的研究中也报道了维替泊芬通过抑制YAP 1而抑制EC的生长并诱导细胞死亡。然而，Verteporfin如何抑制YAP 1的功能的机制仍不清楚。在这项研究中，我们分析了维替泊芬对细胞功能的整体影响，通过使用反相蛋白质阵列（RPPA）和不稳定性通路分析（IPA）。此外，我们首次证明了维替泊芬诱导了YAP 1的SUMO化。有趣的是，我们发现YAP 1的SUMO化受到YAP 1磷酸化的调节。总之，我们的研究揭示了维替泊芬通过调节YAP 1 SUMO化抑制YAP 1功能的新机制。我们的研究可能为Verteporfin通过靶向YAP 1在子宫内膜癌中的临床应用提供理论基础。
Yes-associated protein (YAP or YAP1) has been proposed to function as an oncogene in most cancers, with nuclear localization of YAP1 correlating with poor prognosis. Photosensitizer Verteporfin has been proven as an inhibitor of YAP1 through preventing the combination of YAP1 with TEA domain transcription factor (TEAD). We showed previously that the total and phospho-levels of YAP1 were related to the clinical characteristics and outcomes in endometrial cancer (EC) patients, and that YAP1 promoted the proliferation and metastasis of EC cells in vitro cell line studies and in animal models. We also reported that Verteporfin inhibited cell growth and induced cell death through inhibiting YAP1 in EC in our previous study. However, the mechanism of how Verteporfin inhibits the function of YAP1 remains unclear. In this study, we analyzed the global effects of Verteporfin on cell function by using Reverse Phase Protein Arrays (RPPA) and Ingenuity Pathway Analysis (IPA). Furthermore, we demonstrated that Verteporfin induced the SUMOylation of YAP1 for the first time. Interestingly, we found that the SUMOylation of YAP1 was regulated by YAP1 phosphorylation. Together, our study revealed a novel mechanism by which Verteporfin inhibits the function of YAP1 through regulating YAP1 SUMOylation. Our study may provide a rationale for the clinical use of Verteporfin in endometrial cancer by targeting YAP1.
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影响因子：
7.3
作者：
Zhang H;Ramakrishnan SK;Triner D;Centofanti B;Maitra D;Győrffy B;Sebolt-Leopold JS;Dame MK;Varani J;Brenner DE;Fearon ER;Omary MB;Shah YM
通讯作者：
Shah YM
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1001/jama.284.13.1640-jfd00008-2-1
发表时间：
2000-10
期刊：
JAMA
影响因子：
--
作者：
J. Henney
通讯作者：
J. Henney
影响因子：
10.5
作者：
Garvin, Alexander J.;Walker, Alexandra K.;Morris, Joanna R.
通讯作者：
Morris, Joanna R.
影响因子：
10.5
作者：
Vassilev, A;Kaneko, KJ;DePamphilis, ML
通讯作者：
DePamphilis, ML