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YAP1 plays a key role of the conversion of normal fibroblasts into cancer-associated fibroblasts that contribute to prostate cancer progression
Journal of Experimental & Clinical Cancer Research ( IF 11.3 ) Pub Date : 2020-02-17 , DOI: 10.1186/s13046-020-1542-z
Tianyu Shen , Yang Li , Shimiao Zhu , Jianpeng Yu , Boya Zhang , Xuanrong Chen , Zheng Zhang , Yuan Ma , Yuanjie Niu , Zhiqun Shang

Cancer-associated fibroblasts (CAFs) are an important part of the tumour microenvironment, and their functions are of great concern. This series of experiments aimed to explore how Yes-associated protein 1 (YAP1) regulates the function of stromal cells and how the normal fibroblasts (NFs) convert into CAFs in prostate cancer (PCa). The effects of conditioned media from different fibroblasts on the proliferation and invasion of epithelial cells TrampC1 were examined. We then analysed the interaction between the YAP1/TEAD1 protein complex and SRC, as well as the regulatory function of the downstream cytoskeletal proteins and actins. A transplanted tumour model was used to explore the function of YAP1 in regulating tumour growth through stromal cells. The relationship between the expression of YAP1 in tumour stromal cells and the clinical characteristics of PCa patients was analysed. The expression level of YAP1 was significantly upregulated in PCa stromal cells. After the expression level of YAP1 was increased, NF was transformed into CAF, enhancing the proliferation and invasion ability of epithelial cells. The YAP1/TEAD1 protein complex had the capability to influence downstream cytoskeletal proteins by regulating SRC transcription; therefore, it converts NF to CAF, and CAF can significantly promote tumour growth and metastasis. The high expression of YAP1 in the tumour stromal cells suggested a poor tumour stage and prognosis in PCa patients. YAP1 can convert NFs into CAFs in the tumour microenvironment of PCa, thus promoting the development and metastasis of PCa. Silencing YAP1 in tumour stromal cells can effectively inhibit tumour growth.

中文翻译:

YAP1在正常成纤维细胞向癌症相关成纤维细胞转化中起关键作用,从而促进前列腺癌的进展

癌症相关的成纤维细胞(CAF)是肿瘤微环境的重要组成部分,其功能备受关注。该系列实验旨在探讨Yes相关蛋白1(YAP1)如何调节基质细胞的功能,以及正常成纤维细胞(NFs)如何在前列腺癌(PCa)中转化为CAF。检查了来自不同成纤维细胞的条件培养基对上皮细胞TrampC1增殖和侵袭的影响。然后,我们分析了YAP1 / TEAD1蛋白复合物和SRC之间的相互作用,以及下游细胞骨架蛋白和肌动蛋白的调节功能。使用移植的肿瘤模型探索YAP1在通过基质细胞调节肿瘤生长中的功能。分析了肿瘤基质细胞中YAP1的表达与PCa患者临床特征之间的关系。在PCa基质细胞中,YAP1的表达水平显着上调。YAP1的表达水平升高后,NF转化为CAF,增强了上皮细胞的增殖和侵袭能力。YAP1 / TEAD1蛋白复合物具有通过调节SRC转录影响下游细胞骨架蛋白的能力。因此,它可以将NF转化为CAF,并且CAF可以显着促进肿瘤的生长和转移。YAP1在肿瘤基质细胞中的高表达提示PCa患者的肿瘤分期和预后较差。YAP1可以在PCa的肿瘤微环境中将NFs转化为CAF,从而促进PCa的发展和转移。
更新日期:2020-04-22
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