Year-end Sale % OFF 
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.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer mortality worldwide
We showed that P300/CBP-associated factor (PCAF) induced autophagy in HCC cells through inhibition of the Akt/mTOR pathway
To make a distinction between these two possibilities, LC3 flux was measured in the presence of 3-MA or bafilomycin A1. 3-MA, a class III PI3K inhibitor blocking autophagosome formation, attenuated PCAF-induced LC3 II accumulation, whereas, PCAF could still cause the accumulation of LC3 II in the presence of bafilomycin A1, a vacuolar-type H+-ATPase inhibitor blocking autophagosome–lysosome fusion (Figure 1c)
Summary
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer mortality worldwide. Because of lack of effective approaches to treatment, late diagnosis and impaired liver function, the prognosis of HCC patients is dismal, with a 5-year survival rate at ~ 15%.1. The downregulation of PCAF in tumor specimens was associated with TNM stage and tumor metastasis and had negative correlations with survival rate after liver resection.[7] we found that PCAF increased histone H4 acetylation and inhibited AKT signaling.[8] Recently, histone deacetylase inhibitors has been found to induce cell autophagy in HCC cells.[9] So we hypothesized a connection between PACF and autophagy in HCC. We showed that PCAF induced autophagy in HCC cells through inhibition of the Akt/mTOR pathway. Our data have shown that PCAF is an attractive candidate for the treatment of HCC and that pharmacological targeting of autophagy provides promise for the management of cancer therapy
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
