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P300/CBP-associated factor (PCAF) inhibits the growth of hepatocellular carcinoma by promoting cell autophagy.
- Source :
-
Cell death & disease [Cell Death Dis] 2016 Oct 06; Vol. 7 (10), pp. e2400. Date of Electronic Publication: 2016 Oct 06. - Publication Year :
- 2016
-
Abstract
- Aberrant autophagic processes have been found to have fundamental roles in the pathogenesis of different kinds of tumors, including hepatocellular carcinoma (HCC). P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), performs its function by acetylating both histone and non-histone proteins. Our previous studies showed that PCAF was downregulated in HCC tissues and its high expression was significantly associated with patient survival after surgery, serving as a prognostic marker. In this study we found that overexpression of PCAF induced autophagy of HCC cells and its knockdown depressed autophagy. As type II programmed cell death, autophagy induced by PCAF-elicited cell death in HCC cells. In vivo experiments confirmed that PCAF-induced autophagy inhibited tumor growth. Subsequent in vitro experiments showed that PCAF promoted autophagy by inhibiting Akt/mTOR signaling pathway. Our findings show that PCAF is a novel modulator of autophagy in HCC, and can serve as an attractive therapeutic strategy of HCC treatment.
- Subjects :
- Adenine analogs & derivatives
Adenine pharmacology
Animals
Apoptosis drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Female
Gene Knockdown Techniques
Humans
Macrolides pharmacology
Mice, Inbred BALB C
Mice, Nude
Oligopeptides pharmacology
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction drug effects
TOR Serine-Threonine Kinases metabolism
Xenograft Model Antitumor Assays
Autophagy drug effects
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular pathology
Liver Neoplasms metabolism
Liver Neoplasms pathology
p300-CBP Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 7
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 27711074
- Full Text :
- https://doi.org/10.1038/cddis.2016.247