Dataset Information

Phosphoinositide-specific phospholipase C?1 inhibition induces autophagy in human colon cancer and hepatocellular carcinoma cells.

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

SUBMITTER: Dai L

PROVIDER: S-EPMC5654964 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Dai Lianzhi L Chen Xiaolei X Lu Xiaohong X Wang Fen F Zhan Yanyan Y Song Gang G Hu Tianhui T Xia Chun C Zhang Bing B

Scientific reports 20171024 1

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 wi ...[more]

PMID: 29066806

Similar Datasets

Project description:Our previous studies indicated that phosphoinositide specific phospholipase C?1 (PLC?1) was involved in autophagy induction in colon and hepatic carcinoma cells. However, whether and how PLC?1 regulation in human lung adenocarcinoma is linked to autophagy remains unclear. Here, we assessed the protein expression of PLC?1 in human lung adenocarcinoma tissue using immunohistochemistry assay and the relationship between PLCG1 and autophagy in The Cancer Genome Atlas Network (TCGA) using Spearman correlation analysis and GSEA software. Furthermore, the interaction between PLC?1 and autophagy-related signal molecules was investigated in human lung adenocarcinoma A549 cells treated with different inhibitors or transduction with lentivirus-mediated PLC?1 gene short-hairpin RNA (shRNA) vectors using MTT, clonogenicity, Transwell migration, RT-PCR, Caspase-3, mitochondrial transmembrane potential, and western blotting assays, as well as transmission electron microscope technique. Additionally, the effect of shRNA/PLC?1 alone or combined with autophagic activator Lithium Chloride (LiCl) on tumor growth and metastasis was measured using immunohistochemistry and assays in A549 xenograft nude mouse model. The results showed that increased PLC?1 expression occurred frequently in human lung adenocarcinoma tissue with higher grades of T in TNM staging classification. PLC?1 significantly enriched in autophagic process and regulation, which negatively regulating autophagy was enriched in higher expression of PLC?1. PLC?1 inhibition partially reduced cell proliferation and migration of A549 cells, with an increased autophagic flux involving alterations of AMPK?, mTOR, and ERK levels. However, PLC?1 inhibition-driven autophagy led to cell death without depending on Caspase-3 and RIP1. Additionally, the abrogation of PLC?1 signaling by shRNA and combination with autophagic activator LiCl could efficaciously suppress tumor growth and metastasis in A549 xenograft nude mice, in combination with a decrease in P62 level. These findings collectively suggest that reduction of cell proliferation and migration by PLC?1 inhibition could be partially attributed to PLC?1 inhibition-driven autophagic cell death (ACD). It highlights the potential role of a combination between targeting PLC?1 and autophagy pathway in anti-tumor therapy, which may be an efficacious new strategy to overcome the autophagy addition of tumor and acquired resistance to current therapy.

Dataset Information

Phosphoinositide-specific phospholipase C?1 inhibition induces autophagy in human colon cancer and hepatocellular carcinoma cells.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets