PCAF inhibits hepatocellular carcinoma metastasis by inhibition of epithelial-mesenchymal transition by targeting Gli-1.

Abstract

UNLABELLED:

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.

• Authors: Qing Li, Zhikui Liu, Meng Xu, Yumo Xue, Bowen Yao, Changwei Dou, Yuli Jia, Yufeng Wang, Kangsheng Tu, Xin Zheng, Yingmin Yao
• Journal: Cancer letters (Cancer Lett) Vol. 375 Issue 1 Pg. 190-198 (May 28 2016) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 26945969 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• GLI1 protein, human
• Transcription Factors
• Zinc Finger Protein GLI1
• p300-CBP Transcription Factors
• p300-CBP-associated factor

Topics

• Animals
• Carcinoma, Hepatocellular (metabolism, mortality, secondary)
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition
• Female
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms (metabolism, mortality, pathology)
• Lung Neoplasms (metabolism, mortality, secondary)
• Male
• Mice, Nude
• Middle Aged
• Neoplasm Transplantation
• Transcription Factors (metabolism)
• Zinc Finger Protein GLI1
• p300-CBP Transcription Factors (physiology)