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Abstract: Epidermal growth factor receptor (EGFR) plays an important role in gastric cancer (GC) progression. Our previous data demonstrated that type II cGMP‐dependent protein kinase (PKG II) could block the EGF‐EGFR axis as well as down‐stream signaling pathways, for example, MAPK, PI3 K, and PLC in GC cells. However, the exact mechanisms of PKG II against cancer remain unclear. Therefore, the present work was to address the above question. Human GC cell line AGS was infected with adenoviral construct encoding cDNA of PKG II (Ad‐PKG II) to up‐regulate PKG II and then treated with 8‐pCPT‐cGMP. Two‐dimensional electrophoresis (2‐DE) was used to analyze the changes of protein expression in the cells. The results showed that 17 proteins had more than twofold changes in EGF‐treated group compared with control. However, Ad‐PKG II could effectively reversed the changes. Furthermore, far upstream element‐binding protein 1 (FUBP1) and MarvelD3 were chosen and PKG II activation reversed EGF/EGFR‐induced up‐regulation of FUBP1 and downregulation of MarvelD3, respectively. MarvelD3 silence effectively abolished the inhibitory effect of PKG II on EGF‐triggered migration. These data indicated that the inhibitory effect of PKG II partially was associated with MarvelD3. [ABSTRACT FROM AUTHOR]

The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) play a key role in signaling pathways in oncogenesis. The overexpression of PDGFs and PDGFRs and the oncogenic alterations of these receptors have been implicated in human cancers and correlated significantly with poor outcomes. This review discusses the biology of the PDGF isoforms and receptors briefly, and their role in oncogenesis. Also, the attractiveness of targeting PDGFs and PDGFRs, based on a wide display of oncologic alterations in cancers, diverse therapeutic strategies, their roles in resistance to cancer treatments with prospects of overcoming drug resistance, and the extent to which validated biomarkers have been developed for effective PDGFs and PDGFRs-based cancer management are discussed. [ABSTRACT FROM AUTHOR]

Background: 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. Methodology/Principal Findings: 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. Conclusion/Significance: 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. [ABSTRACT FROM AUTHOR]