Li Qing, Liu Zhikui, Xu Meng, Xue Yumo, Yao Bowen, Dou Changwei, Jia Yuli, Wang Yufeng, Tu Kangsheng, Zheng Xin, Yao Yingmin
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Cancer Lett. 2016 May 28;375(1):190-198. doi: 10.1016/j.canlet.2016.02.053. Epub 2016 Mar 2.
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.
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.
p300-CBP相关因子(PCAF)除具有组蛋白乙酰转移酶(HAT)活性外,还具有内在的泛素化活性,该活性参与多种转录调节因子,包括转录因子胶质瘤相关癌基因1(Gli1),它是癌症中上皮-间质转化(EMT)的著名调节因子。在本研究中,我们检测到与相邻非肿瘤组织相比,PCAF在肝细胞癌(HCC)组织中表达下调,并且与HCC患者的恶性门静脉侵犯(p < 0.05)和不良生存(p < 0.05)显著相关。此外,功能研究表明,PCAF的下调促进肿瘤细胞通过EMT迁移和侵袭。进一步研究发现,Gli1作为PCAF的直接靶点诱导EMT并促进肿瘤转移和侵袭。
PCAF是一种抑癌基因,通过靶向Gli1抑制HCC细胞转移和EMT,在HCC发生发展中起重要作用,这表明PCAF在抑制HCC转移方面具有潜在的治疗价值。