title: DAG/PKCδ and IP3/Ca²⁺/CaMK IIβ Operate in Parallel to Each Other in PLCγ1-Driven Cell Proliferation and Migration of Human Gastric Adenocarcinoma Cells, through Akt/mTOR/S6 Pathway.
abstract: Phosphoinositide specific phospholipase Cγ (PLCγ) activates diacylglycerol (DAG)/protein kinase C (PKC) and inositol 1,4,5-trisphosphate (IP3)/Ca(2+)/calmodulin-dependent protein kinase II (CaMK II) axes to regulate import events in some cancer cells, including gastric adenocarcinoma cells. However, whether DAG/PKCδ and IP3/Ca(2+)/CaMK IIβ axes are simultaneously involved in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells and the underlying mechanism are not elucidated. Here, we investigated the role of DAG/PKCδ or CaMK IIβ in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells, using the BGC-823 cell line. The results indicated that the inhibition of PKCδ and CaMK IIβ could block cell proliferation and migration of BGC-823 cells as well as the effect of inhibiting PLCγ1, including the decrease of cell viability, the increase of apoptotic index, the down-regulation of matrix metalloproteinase (MMP) 9 expression level, and the decrease of cell migration rate. Both DAG/PKCδ and CaMK IIβ triggered protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/S6 pathway to regulate protein synthesis. The data indicate that DAG/PKCδ and IP3/Ca(2+)/CaMK IIβ operate in parallel to each other in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells through Akt/mTOR/S6 pathway, with important implication for validating PLCγ1 as a molecular biomarker in early gastric cancer diagnosis and disease surveillance.
authors.affiliation: Medical School, Xiamen University, Fujian 361102, China. 24520131153431@stu.xmu.edu.cn.
authors.forename: Lianzhi
authors.initials: L
authors.lastname: Dai
authors.affiliation: Medical School, Xiamen University, Fujian 361102, China. zhuangluhua@gmail.com.
authors.forename: Luhua
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: Medical School, Xiamen University, Fujian 361102, China. bczhang@foxmail.com.
authors.forename: Bingchang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Medical School, Xiamen University, Fujian 361102, China. 24520141153450@stu.xmu.edu.cn.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Zhongshan Hospital, Xiamen University, Fujian 361004, China. cxl910904@gmail.com.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Zhongshan Hospital, Xiamen University, Fujian 361004, China. chunxia@xmu.edu.cn.
authors.forename: Chun
authors.initials: C
authors.lastname: Xia
authors.affiliation: Medical School, Xiamen University, Fujian 361102, China. cristal66@xmu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004075:Diglycerides / Q000378:metabolism; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D051379:Mice; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D051966:Phospholipase C gamma; D002118:Calcium
keywords: Akt/mTOR/S6; DAG/PKCδ; IP3/Ca2+/CaMK IIβ; PLCγ1; cell proliferation; human gastric adenocarcinoma cells; migration