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Int. J. Mol. Sci. 2015, 16(12), 28510-28522; doi:10.3390/ijms161226116

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

1
Medical School, Xiamen University, Fujian 361102, China
2
Zhongshan Hospital, Xiamen University, Fujian 361004, China
*
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 27 October 2015 / Revised: 15 November 2015 / Accepted: 20 November 2015 / Published: 1 December 2015
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)
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Abstract

Phosphoinositide specific phospholipase Cγ (PLCγ) activates diacylglycerol (DAG)/protein kinase C (PKC) and inositol 1,4,5-trisphosphate (IP3)/Ca2+/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/Ca2+/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/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, with important implication for validating PLCγ1 as a molecular biomarker in early gastric cancer diagnosis and disease surveillance. View Full-Text
Keywords: PLCγ1; DAG/PKCδ; IP3/Ca2+/CaMK IIβ; Akt/mTOR/S6; cell proliferation; migration; human gastric adenocarcinoma cells PLCγ1; DAG/PKCδ; IP3/Ca2+/CaMK IIβ; Akt/mTOR/S6; cell proliferation; migration; human gastric adenocarcinoma cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Dai, L.; Zhuang, L.; Zhang, B.; Wang, F.; Chen, X.; Xia, C.; Zhang, B. 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. Int. J. Mol. Sci. 2015, 16, 28510-28522.

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