PKG II inhibits EGF/EGFR-induced migration of gastric cancer cells

• Published in: PloS one 2013-04, Vol.8 (4), p.e61674-e61674
• Main Authors: Jiang, Lu, Lan, Ting, Chen, Yongchang, Sang, Jianrong, Li, Yueying, Wu, Min, Tao, Yan, Wang, Ying, Qian, Hai, Gu, Luo
• Format: Article
• Language: English
• Subjects: Activation; Apoptosis; Biology; Blocking; Cancer; Cancer cells; Cancer therapies; Cell adhesion & migration; Cell Line; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Movement - genetics; Cellular signal transduction; Cyclic GMP; Cyclic GMP - analogs & derivatives; Cyclic GMP-Dependent Protein Kinase Type II - genetics; Cyclic GMP-Dependent Protein Kinase Type II - metabolism; Epidermal growth factor; Epidermal Growth Factor - pharmacology; Epidermal growth factor receptors; Epidermal growth factors; Extracellular signal-regulated kinase; G proteins; Gastric cancer; Humans; Inhibition; Kinases; Laboratories; Ligands; MAP kinase; Medical research; Medicine; Pathways; Phosphorylation; Phosphorylation - drug effects; Phosphorylation - genetics; Physiology; Protein kinase; Protein kinases; Proteins; Rac1 protein; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Science; Signal transduction; Signal Transduction - drug effects; Signal Transduction - genetics; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Studies; Thionucleotides; Threonine; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0061674

Our previous research results showed that Type II cGMP dependent protein kinase (PKG II) could block the activation of epidermal growth factor receptor (EGFR) and consequently inhibit the proliferation and the related MAPK/ERK-mediated signal transduction of gastric cancer cell line BGC-823, suggesting that PKG II might inhibit other EGFR-triggered signal transduction pathways and related biological activities of gastric cancer cells. This paper was designed to investigate the potential inhibition of PKG II on EGF/EGFR-induced migration activity and the related signal transduction pathways. In gastric cancer cell line AGS, expression and activity of PKG II were increased by infecting the cells with adenoviral construct encoding PKG II cDNA (Ad-PKG II) and treating the cells with cGMP analogue 8-pCPT-cGMP. Phosphorylation of proteins was detected by Western Blotting and active small G protein Ras and Rac1 was measured by "Pull-down" method. Cell migration activity was detected with trans-well equipment. Binding between PKG II and EGFR was detected with Co-IP. The results showed EGF stimulated migration of AGS cell and the effect was related to PLCγ1 and ERK-mediated signal transduction pathways. PKG II inhibited EGF-induced migration activity and blocked EGF-initiated signal transduction of PLCγ1 and MAPK/ERK-mediated pathways through preventing EGF-induced Tyr 992 and Tyr 1068 phosphorylation of EGFR. PKG II bound with EGFR and caused threonine phosphorylation of it. Our results systemically confirms the inhibition of PKG II on EGF-induced migration and related signal transduction of PLCγ1 and MAPK/ERK-mediated pathways, indicating that PKG II has a fargoing inhibition on EGF/EGFR related signal transduction and biological activities of gastric cancer cells through phosphorylating EGFR and blocking the activation of it.