Phosphoinositide-specific phospholipase Cγ1 inhibition induces autophagy in human colon cancer and hepatocellular carcinoma cells

Phosphoinositide-specific phospholipase C (PLC)gamma 1 has been reported to be involved in cancer cell proliferation and metastasis. However, whether PLC gamma 1 modulates autophagy and the underlying mechanism remains unclear. Here, we investigated the relationship between PLC gamma 1 and autophagy in the human colon cancer cell line HCT116 and hepatocellular carcinoma cell line HepG2. The results indicated that PLC gamma 1 inhibition via lentivirus-mediated transduction with shRNA/PLC gamma 1 or transient transfection with pRK5-PLC gamma 1 (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 PLC gamma 1 inhibition by blocking the FAK/PLC gamma 1 axis. In addition, PLC gamma 1 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 PLC gamma 1 inhibition induced autophagy and the FAK/PLC gamma 1 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 PLC gamma 1 inhibition. Consequently, these findings provide novel insight into autophagy regulation by PLC gamma 1 in colon cancer and hepatocellular carcinoma cells.