PCAF inhibits hepatocellular carcinoma metastasis by inhibition of epithelial-mesenchymal transition by targeting Gli-1. Issue 1 (28th May 2016)

• Record Type: Journal Article
• Authors: Li, Qing; Liu, Zhikui; Xu, Meng; Xue, Yumo; Yao, Bowen; Dou, Changwei; Jia, Yuli; Wang, Yufeng; Tu, Kangsheng; Zheng, Xin; Yao, Yingmin
• Is Part Of: Cancer letters. Volume 375:Issue 1(2016)
• Page Start: 190
• Page End: 198
• Publication Date: 2016-05-28
• Subjects: Hepatocellular carcinoma -- EMT -- PCAF -- Tumor invasion -- Gli1; HCC hepatocellular carcinoma -- HAT histone acetyltransferase -- PCAF p300–CBP-associated factor -- Gli1 transcription factor glioma-associated oncogene 1 -- EMT epithelial–mesenchymal transition -- H&E hematoxylin and eosin -- IHC Immunohistochemical staining -- NC siRNA scramble siRNAs -- PVTT portal vein tumor thrombus -- T HCC primary tumor -- NT peri-cancerous tissues; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.02.053
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: PCAF is low-expressed in 51.4% of resected HCC tissues by immunohistochemistry. Clinicopathological data showed decreased PCAF was associated with HCC metastasis. PCAF may inhibit HCC metastasis through induced EMT via modulating Gli1 expression. Abstract: 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.