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MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.

Sun L, Liu L, Liu X, Wang Y, Li M, Yao L, Yang J, Ji G, Guo C, Pan Y, Liang S, Wang B, Ding J, Zhang H, Shi Y - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

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Related in: MedlinePlus

Characterization of the interaction between MGr1-Ag/37LRP and phosphorylated focal adhesion kinase (pFAK) in the condition of adhesion to laminin (LN). (a) Western blot analysis detected the expression of MGr1-Ag/37LRP, pFAK and total FAK (tFAK) in SGC7901 gastric cancer cells in the condition of adhesion to LN at the indicated concentration. (b) Western blot analysis detected pFAK and tFAK expression in transfected cells that expressed up- or downregulated MGr1-Ag/37LRP after adhesion to LN and BSA control. (c) Immunoprecipitation detected the interaction between MGr1-Ag/37LRP and pFAK in SGC7901/VCR and SGC7901 in adhesion to LN or control.
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fig02: Characterization of the interaction between MGr1-Ag/37LRP and phosphorylated focal adhesion kinase (pFAK) in the condition of adhesion to laminin (LN). (a) Western blot analysis detected the expression of MGr1-Ag/37LRP, pFAK and total FAK (tFAK) in SGC7901 gastric cancer cells in the condition of adhesion to LN at the indicated concentration. (b) Western blot analysis detected pFAK and tFAK expression in transfected cells that expressed up- or downregulated MGr1-Ag/37LRP after adhesion to LN and BSA control. (c) Immunoprecipitation detected the interaction between MGr1-Ag/37LRP and pFAK in SGC7901/VCR and SGC7901 in adhesion to LN or control.

Mentions: As FAK was a very important signal molecule associated with CAM-DR in many tumors, we first examined the phosphorylated FAK (pFAK) and total FAK (tFAK) expression in the SGC7901 cell adhesion to LN and BSA. Western blot analysis revealed expression of both MGr1-Ag/37LRP and pFAK at dose-dependent increases in SGC7901 induced by adhesion to LN at indicated concentration (Fig.2a). We then detected the pFAK and tFAK expression in the GC transfected cells that expressed up- or downregulated MGr1-Ag/37LRP after adhesion to ECM components and control. As shown in Figure2(b), the expression of pFAK in SGC7901-MGr1 after adhesion to LN significantly increased compared to that of SGC7901 and SGC7901-pc in the same conditions, and the expression of pFAK in SGC7901-MGr1 after adhesion to LN significantly increased compared to that of the same cells' adhesion to BSA. In addition, compared to the weak expression of pFAK in SGC7901-MGr1, the expression of pFAK could not be detected in SGC7901-pc or SGC7901 cells after adhesion to control. The expression of pFAK in SGC7901/VCR-siMGr1 after adhesion to ECM components and control significantly decreased compared to that of SGC7901/VCR and SGC7901/VCR-ps in the same conditions. As shown in Figure2(c), immunoprecipitation was recruited to evaluate the interaction between MGr1-Ag/37LRP and pFAK in the condition of adhesion to LN and control. Only in GC MDR variants SGC7901/VCR in adhesion to control, there was an interaction between MGr1-Ag/37LRP and pFAK. In adhesion to LN, there were different interactions between MGr1-Ag/37LRP and pFAK in both GC MDR variant SGC7901/VCR and drug-sensitive cells SGC7901. It was concluded that, as the receptor of ECM components, MGr1-Ag/37LRP may activate the downstream signal pathway through interaction with pFAK.


MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.

Sun L, Liu L, Liu X, Wang Y, Li M, Yao L, Yang J, Ji G, Guo C, Pan Y, Liang S, Wang B, Ding J, Zhang H, Shi Y - Cancer Sci. (2014)

Characterization of the interaction between MGr1-Ag/37LRP and phosphorylated focal adhesion kinase (pFAK) in the condition of adhesion to laminin (LN). (a) Western blot analysis detected the expression of MGr1-Ag/37LRP, pFAK and total FAK (tFAK) in SGC7901 gastric cancer cells in the condition of adhesion to LN at the indicated concentration. (b) Western blot analysis detected pFAK and tFAK expression in transfected cells that expressed up- or downregulated MGr1-Ag/37LRP after adhesion to LN and BSA control. (c) Immunoprecipitation detected the interaction between MGr1-Ag/37LRP and pFAK in SGC7901/VCR and SGC7901 in adhesion to LN or control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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fig02: Characterization of the interaction between MGr1-Ag/37LRP and phosphorylated focal adhesion kinase (pFAK) in the condition of adhesion to laminin (LN). (a) Western blot analysis detected the expression of MGr1-Ag/37LRP, pFAK and total FAK (tFAK) in SGC7901 gastric cancer cells in the condition of adhesion to LN at the indicated concentration. (b) Western blot analysis detected pFAK and tFAK expression in transfected cells that expressed up- or downregulated MGr1-Ag/37LRP after adhesion to LN and BSA control. (c) Immunoprecipitation detected the interaction between MGr1-Ag/37LRP and pFAK in SGC7901/VCR and SGC7901 in adhesion to LN or control.
Mentions: As FAK was a very important signal molecule associated with CAM-DR in many tumors, we first examined the phosphorylated FAK (pFAK) and total FAK (tFAK) expression in the SGC7901 cell adhesion to LN and BSA. Western blot analysis revealed expression of both MGr1-Ag/37LRP and pFAK at dose-dependent increases in SGC7901 induced by adhesion to LN at indicated concentration (Fig.2a). We then detected the pFAK and tFAK expression in the GC transfected cells that expressed up- or downregulated MGr1-Ag/37LRP after adhesion to ECM components and control. As shown in Figure2(b), the expression of pFAK in SGC7901-MGr1 after adhesion to LN significantly increased compared to that of SGC7901 and SGC7901-pc in the same conditions, and the expression of pFAK in SGC7901-MGr1 after adhesion to LN significantly increased compared to that of the same cells' adhesion to BSA. In addition, compared to the weak expression of pFAK in SGC7901-MGr1, the expression of pFAK could not be detected in SGC7901-pc or SGC7901 cells after adhesion to control. The expression of pFAK in SGC7901/VCR-siMGr1 after adhesion to ECM components and control significantly decreased compared to that of SGC7901/VCR and SGC7901/VCR-ps in the same conditions. As shown in Figure2(c), immunoprecipitation was recruited to evaluate the interaction between MGr1-Ag/37LRP and pFAK in the condition of adhesion to LN and control. Only in GC MDR variants SGC7901/VCR in adhesion to control, there was an interaction between MGr1-Ag/37LRP and pFAK. In adhesion to LN, there were different interactions between MGr1-Ag/37LRP and pFAK in both GC MDR variant SGC7901/VCR and drug-sensitive cells SGC7901. It was concluded that, as the receptor of ECM components, MGr1-Ag/37LRP may activate the downstream signal pathway through interaction with pFAK.

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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

Show MeSH
Related in: MedlinePlus