Yes-associated protein 1 (YAP1) promotes human gallbladder tumor growth via activation of the AXL/MAPK pathway
Yes-associated protein 1 (YAP1) promotes human gallbladder tumor growth via activation of the AXL/MAPK pathway
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Yes 相关蛋白 1 (YAP1) 通过激活 AXL/MAPK 通路促进人胆囊肿瘤生长
DOI：
10.1016/j.canlet.2014.08.036
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发表时间：
2014-12-28
期刊：
影响因子：
9.7
通讯作者：
Liu, Yingbin
中科院分区：
文献类型：
--
作者：
Li, Maolan;Lu, Jianhua;Liu, Yingbin
转录共激活因子 Yes 相关蛋白 1 (YAP1) 是脊椎动物细胞增殖和器官大小的关键调节因子，与多种恶性肿瘤有关。然而，人们对YAP1在人胆囊癌（GBC）中的表达和生物学功能知之甚少。在本研究中，我们研究了YAP1在GBC中的临床意义和生物学功能，发现核YAP1及其靶基因AXL在GBC组织中过表达。我们还观察到 YAP1 和 AXL 高表达水平与较差的预后之间存在显着相关性。使用慢病毒 shRNA 敲除 YAP1 可诱导细胞周期停滞在 S 期，从而显着抑制细胞增殖，与 CDK2、CDC25A 和细胞周期蛋白 A 的减少一致，并导致 GBC 细胞系体外细胞凋亡增加和侵袭性抑制。此外，YAP1 的敲低也抑制了体内肿瘤的生长。此外，我们证明 AXL/MAPK 通路的激活参与 GBC 中 YAP1 的致癌功能。这些结果表明，YAP1 是一种假定的癌基因，代表一种预后标志物，并且可能是 GBC 的新治疗靶点。 (C) 2014 Elsevier Ireland Ltd. 保留所有权利。
The transcriptional coactivator Yes-associated protein 1 (YAP1), a key regulator of cell proliferation and organ size in vertebrates, has been implicated in various malignancies. However, little is known about the expression and biological function of YAP1 in human gallbladder cancer (GBC). In this study we examined the clinical significance and biological functions of YAP1 in GBC and found that nuclear YAP1 and its target gene AXL were overexpressed in GBC tissues. We also observed a significant correlation between high YAP1 and AXL expression levels and worse prognosis. The depletion of YAP1 using lentivirus shRNAs significantly inhibited cell proliferation by inducing cell cycle arrest in S phase in concordance with the decrease of CDK2, CDC25A, and cyclin A, and resulted in increased cell apoptosis and invasive repression in GBC cell lines in vitro. Furthermore, knockdown of YAP1 also inhibited tumor growth in vivo. Additionally, we demonstrated that the activation of the AXL/MAPK pathway was involved in the oncogenic functions of YAP1 in GBC. These results demonstrated that YAP1 is a putative oncogene and represents a prognostic marker and potentially a novel therapeutic target for GBC. (C) 2014 Elsevier Ireland Ltd. All rights reserved.