文章基本信息

标题：Phosphoinositide-specific phospholipase Cγ1 inhibition induces autophagy in human colon cancer and hepatocellular carcinoma cells
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作者：Lianzhi Dai ; Xiaolei Chen ; Xiaohong Lu 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-13334-y
语种：English
出版社：Springer Nature
摘要：Phosphoinositide-specific phospholipase C (PLC) γ1 has been reported to be involved in cancer cell proliferation and metastasis. However, whether PLCγ1 modulates autophagy and the underlying mechanism remains unclear. Here, we investigated the relationship between PLCγ1 and autophagy in the human colon cancer cell line HCT116 and hepatocellular carcinoma cell line HepG2. The results indicated that PLCγ1 inhibition via lentivirus-mediated transduction with shRNA/PLCγ1 or transient transfection with pRK5-PLCγ1 (Y783A) vector increased LC3B-II levels and the number of autophagic vacuoles and decreased p62 levels. Addition of an autophagy inhibitor led to LC3B and p62 accumulation. Furthermore, AMPK activation promoted the autophagy induced by PLCγ1 inhibition by blocking the FAK/PLCγ1 axis. In addition, PLCγ1 inhibition either blocked the mTOR/ULK1 axis or enhanced dissociation of the Beclin1-IP3R-Bcl-2 complex to induce autophagy. Taken together, our findings revealed that PLCγ1 inhibition induced autophagy and the FAK/PLCγ1 axis is a potential downstream effector of the AMPK activation-dependent autophagy signalling cascade. Both blockade of the mTOR/ULK1 axis and dissociation of the Beclin1-IP3R-Bcl-2 complex contributed to the induction of autophagy by PLCγ1 inhibition. Consequently, these findings provide novel insight into autophagy regulation by PLCγ1 in colon cancer and hepatocellular carcinoma cells.