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

Cancer Lett. 2016 May 28;375(1):190-198. doi: 10.1016/j.canlet.2016.02.053. Epub 2016 Mar 2.

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.

Keywords: EMT; Gli1; Hepatocellular carcinoma; PCAF; Tumor invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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