YAP is a critical oncogene in human cholangiocarcinoma.
YAP is a critical oncogene in human cholangiocarcinoma.
复制标题
YAP 是人类胆管癌的关键癌基因
DOI：
10.18632/oncotarget.4043
复制
发表时间：
2015-07-10
期刊：
影响因子：
--
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Pei T;Li Y;Wang J;Wang H;Liang Y;Shi H;Sun B;Yin D;Sun J;Song R;Pan S;Sun Y;Jiang H;Zheng T;Liu L
是相关蛋白（雅普）是一种转录辅激活因子，在细胞信号转导中具有重要的调节作用，在许多癌症中表达异常。然而，雅普在胆管癌（CCA）进展中的作用仍不清楚。在这里，我们证明了雅普在CCA细胞和人体标本中过表达。核雅普（n雅普）高表达与CCA的分化程度、TNM分期、转移及预后不良有关。在体内和体外，沉默雅普增加了肿瘤对化疗的敏感性，并抑制了CCA肿瘤的发生和转移。雅普在体内和体外的过表达促进了CCA肿瘤的发生和转移。另外，我们发现雅普可诱导上皮-间充质转化（EMT），并与miR-29 c、IGF 1、AKT和Gankyrin形成调控回路，促进CCA的进展。CCA组织芯片结果显示nYAP与gankyrin和p-AKT表达呈正相关。nYAP和gankyrin或p-AKT的组合表现出改善的CCA患者的预后准确性。总之，雅普通过激活AKT途径上调Gankyrin促进癌的发生和转移。
Yes-associated protein (YAP), a transcriptional co-activator, has important regulatory roles in cell signaling and is dysregulated in a number of cancers. However, the role of YAP in cholangiocarcinoma (CCA) progression remains unclear. Here, we demonstrated that YAP was overexpressed in CCA cells and human specimens. High levels of nuclear YAP (nYAP) correlated with histological differentiation, TNM stage, metastasis and poor prognosis in CCA. Silencing YAP increased tumor sensitivity to chemotherapy and inhibited CCA tumorigenesis and metastasis both in vivo and in vitro. YAP overexpression in vivo and in vitro promoted CCA tumorigenesis and metastasis. Additionally, we found that YAP induced epithelial-mesenchymal transition (EMT) and formed a regulatory circuit with miR-29c, IGF1, AKT and gankyrin to promote the progression of CCA. Results of CCA tissue microarray showed positive correlations between nYAP and gankyrin or p-AKT expression. Combination of nYAP and gankyrin or p-AKT exhibited improved prognostic accuracy for CCA patients. In conclusion, YAP promotes carcinogenesis and metastasis by up-regulating gankyrin through activation of the AKT pathway.