Metastasis of human gastric adenocarcinoma partly depends on phosphoinositide-specific phospholipase γ1 expression

It is known that phosphoinositide-specific phospholipases gamma 1 (PLC gamma 1) can trigger several signalling pathways to regulate cell proliferation, differentiation, and metastasis. However, whether this kinase is highly expressive and active in human gastric adenocarcinomas, and whether it can play an important role in the development of the cancer, have not yet been investigated. The aim of the study was to investigate the expression of PLC gamma 1 in human gastric adenocarcinoma, while the question of whether PLC gamma 1 can be activated through protein kinase B (Akt) signalling pathways to regulate cell migration was further explored using human gastric adenocarcinoma BGC-823 cell line. The expression of PLC gamma 1 in human adenocarcinoma was detected using immunohistochemical staining. The BGC-823 cells were cultured and treated with inhibitors or transfected with plasmid construction. The cell migration of BGC-823 cells was measured with wound healing assay, cell migration assay, and the ruffling assay. The expression levels of PLC gamma 1 and its related signal molecules in BGC-823 cells were assessed using Western blot analysis or gelatine zymography assay. PLC gamma 1 was highly expressed in human gastric adenocarcinomas, especially in the region with lymph node metastasis. It was shown that migration of BGC-823 cells in vitro depends on PLC gamma 1 activation. This activation is mediated through Akt, an upstream of PLC gamma 1 that triggers the PLC gamma 1/extracellular signal-regulated kinase (ERK)/matrix metalloproteinase (MMP) pathway in BGC-823 cells. PLC gamma 1 activities play an important role in the metastasis of gastric adenocarcinoma, and may serve as a potential therapeutic target in this type of cancer.