PCAF inhibits hepatocellular carcinoma metastasis by inhibition of epithelial-mesenchymal transition by targeting Gli-1
PCAF inhibits hepatocellular carcinoma metastasis by inhibition of epithelial-mesenchymal transition by targeting Gli-1
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PCAF 通过靶向 Gli-1 抑制上皮间质转化，从而抑制肝细胞癌转移。
DOI：
10.1016/j.canlet.2016.02.053
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发表时间：
2016-05-28
期刊：
影响因子：
9.7
通讯作者：
Yao, Yingmin
中科院分区：
文献类型：
--
作者：
Li, Qing;Liu, Zhikui;Yao, Yingmin
p300-CBP相关因子（PCAF），除了其组蛋白乙酰转移酶（HAT）活性外，还具有内在的泛素化活性，参与各种转录调节因子，包括转录因子胶质瘤相关癌基因1（Gli 1），一种众所周知的癌症上皮-间质转化（EMT）调节因子。在本研究中，我们检测到PCAF在肝细胞癌（HCC）组织中表达较癌旁组织下调，并且与HCC患者的恶性门静脉侵犯（p < 0.05）和低生存率（p < 0.05）显著相关。此外，功能研究表明，下调PCAF可促进肿瘤细胞的迁移，通过EMT侵袭。进一步的研究发现Gli 1作为PCAF的直接靶点，可诱导EMT，促进肿瘤的转移和侵袭。结论：PCAF是一种抑癌基因，通过靶向Gli 1抑制肝癌细胞的转移和EMT，在肝癌的发生发展中起重要作用，提示PCAF对肝癌转移具有潜在的治疗价值。(C)2016爱思唯尔爱尔兰有限公司版权所有。
The p300-CBP-associated factor (PCAF), other than its histone acetyltransferase (HAT) activity, possesses an intrinsic ubiquitination activity that is involved in various transcriptional regulators, including the transcription factor glioma-associated oncogene 1 (Gli1), a well-known regulator of epithelial-mesenchymal transition (EMT) in cancer. In present research, we detected that PCAF was down regulated in hepatocellular carcinoma (HCC) tissues compared with the adjacent non-tumor tissues and significantly associated with malignant portal vein invasion (p < 0.05) and poor survival (p < 0.05) of HCC patients. Moreover, functional study demonstrated that downregulation of PCAF facilitated tumor cell migration, invasion via EMT. Further study found that Gli1 as a direct target of PCAF induced EMT and promoted tumor metastasis and invasion. Conclusion: PCAF is an anti-oncogene that plays an important role in the development of HCC by suppressing HCC cell metastasis and EMT by targeting Gli1, which indicates the potential therapeutic value of PCAF for suppression of metastasis of HCC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.