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

Abstract

It is known that phosphoinositide-specific phospholipases γ1(PLCγ1) 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 PLCγ1 in human gastric adenocarcinoma, while the question of whether PLCγ1 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 PLCγ1 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 PLCγ1 and its related signal molecules in BGC-823 cells were assessed using Western blot analysis or gelatine zymography assay. PLCγ1 was highly expressed in humangastric adenocarcinomas, especially in the region with lymph node metastasis. It was shown that migration of BGC-823 cells in vitro depends on PLCγ1 activation. This activation is mediated through Akt, an upstream of PLCγ1 that triggers the PLCγ1/extracellular signal-regulated kinase (ERK)/matrix metalloproteinase (MMP) pathway in BGC-823 cells. PLCγ1 activities play an important role in the metastasis of gastric adenocarcinoma, and may serve as a potential therapeutic target in this type of cancer.