[致癌性YAP在肝癌发生中的非自主效应]
[Nonautonomous effects of oncogenic YAP in hepatocarcinogenesis].
作者信息
Marquard S, Thomann S, Weiler S M E, Sticht C, Gretz N, Schirmacher P, Breuhahn K
机构信息
Pathologisches Institut Heidelberg, Universität Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland.
Medizinische Fakultät Mannheim, Medical Research Center, Universität Heidelberg, Mannheim, Deutschland.
出版信息
Pathologe. 2017 Nov;38(Suppl 2):175-179. doi: 10.1007/s00292-017-0361-2.
BACKGROUND
The transcriptional coactivator yes-associated protein (YAP) is a strong oncogene in liver cancer development.
OBJECTIVES
To investigate if and how YAP-induced paracrine-acting factors are regulated in hepatocytes and liver cancer cells.
MATERIAL AND METHODS
Transcriptome analysis and proteomics of murine wildtype and YAP-transgenic hepatocytes were performed to identify paracrine-acting proteins. Molecular and biochemical techniques were used to examine the mechanisms of YAP-dependent gene regulation. Gene expression data from HCC (hepatocellular carcinoma) patients was evaluated.
RESULTS
Several YAP-dependent, secreted factors (e. g. CXCL10, GDF15, PDGFB) were identified. YAP regulates these factors through transcription factors of the TEAD (TEA domain) protein family. Moreover, the dysregulation of the YAP-target genes is often associated with poor HCC patient prognosis.
CONCLUSIONS
YAP induces the expression of paracrine-acting factors that may affect the tumor microenvironment and therefore support carcinogenesis. This multicellular network could allow the development of novel and specific perturbation approaches.
背景
转录共激活因子Yes相关蛋白（YAP）是肝癌发生过程中的一种强致癌基因。
目的
研究YAP诱导的旁分泌作用因子在肝细胞和肝癌细胞中是否以及如何受到调控。
材料与方法
对小鼠野生型和YAP转基因肝细胞进行转录组分析和蛋白质组学研究，以鉴定旁分泌作用蛋白。采用分子和生化技术检测YAP依赖性基因调控的机制。评估来自肝细胞癌（HCC）患者的基因表达数据。
结果
鉴定出几种YAP依赖性分泌因子（如CXCL10、GDF15、PDGFB）。YAP通过TEA结构域（TEAD）蛋白家族的转录因子调控这些因子。此外，YAP靶基因的失调通常与HCC患者预后不良相关。
结论
YAP诱导旁分泌作用因子的表达，这些因子可能影响肿瘤微环境，从而支持肿瘤发生。这种多细胞网络可能有助于开发新的特异性干扰方法。
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