MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.
Bottom Line: However, the MGr1-Ag-initiated intracellular signal transduction pathway is still unknown.Further study found that, as a receptor of ECM components, MGr1-Ag/37LRP may activate the downstream signal pathway PI3K/AKT and MAPK/ERK through interaction with phosphorylated FAK.Moreover, the sensitivity to chemotherapeutic drugs could be significantly enhanced by inhibiting MGr1-Ag/37LRP expression through mAbs, siRNA, and antisense oligonucleotide.
Affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.Show MeSH
Related in: MedlinePlus
Mentions: We found that LN- and exogenous MGr1-Ag/37LRP could induce phosphorylation of FAK in GC cells. As the survival pathways of PI3K/AKT and MEK/ERK1/2 could be activated by pFAK. We previously reported that MGr1-Ag overexpression could increase expression of Bcl-2 protein. So, we examined whether LN and exogenous MGr1-Ag/37LRP induced the upregulation of Bcl-2 through activation of the PI3K/AKT and MEK/ERK1/2 signaling pathways by Western blot analysis. As shown in Figure3, exogenous MGr1-Ag/37LRP and LN substrate could greatly increase AKT and ERK1/2 phosphorylation in SGC7901 cells. Transient transfection of cells with MGr1-Ag/37LRP or FAK siRNA partly blocked LN-induced AKT and ERK1/2 phosphorylation and inhibited LN-induced Bcl-2 expression. In addition, treatment with PI3K-specific inhibitor LY294002 and MEK1/2-specific inhibitor U0126 could block LN-induced AKT and ERK1/2 phosphorylation, respectively, and inhibited LN-induced Bcl-2 expression. It was concluded that LN- and exogenous MGr1-Ag/37LRP induced Bcl-2 expression may partly through signal pathway FAK-PI3K/Akt and MEK/ERK1/2.
Affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.