P300/CBP-associated factor (PCAF) inhibits the growth of hepatocellular carcinoma by promoting cell autophagy.
P300/CBP-associated factor (PCAF) inhibits the growth of hepatocellular carcinoma by promoting cell autophagy.
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P300/CBP相关因子（PCAF）通过促进细胞自噬抑制肝细胞癌的生长。
DOI：
10.1038/cddis.2016.247
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发表时间：
2016-10-06
影响因子：
9
通讯作者：
Liu QG
中科院分区：
文献类型：
--
作者：
Jia YL;Xu M;Dou CW;Liu ZK;Xue YM;Yao BW;Ding LL;Tu KS;Zheng X;Liu QG
异常的自噬过程在包括肝细胞癌（HCC）在内的多种肿瘤的发病机制中起着重要作用。P300/CBP相关因子（PCAF）是一种组蛋白乙酰转移酶（HAT），通过乙酰化组蛋白和非组蛋白蛋白来发挥其功能。我们以前的研究表明，PCAF在HCC组织中下调，其高表达与患者术后生存率显著相关，可作为预后标志物。在本研究中，我们发现PCAF的过表达诱导肝癌细胞的自噬，其敲低抑制自噬。自噬作为II型程序性细胞死亡，在肝癌细胞中由PCAF诱导的细胞死亡。体内实验证实，PCAF诱导的自噬抑制肿瘤生长。随后的体外实验表明PCAF通过抑制Akt/mTOR信号通路促进自噬。我们的研究结果表明，PCAF是一种新的肝癌自噬调节剂，可以作为一个有吸引力的肝癌治疗策略。
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.
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影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
9.2
作者：
Bannister, AJ;Miska, EA;Kouzarides, T
通讯作者：
Kouzarides, T
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作者：
Kroemer G;Mariño G;Levine B
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Levine B
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作者：
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作者：
Noda, T;Ohsumi, Y
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Ohsumi, Y