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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Mechanism study of peptide GMBP1 and its receptor GRP78 in modulating gastric cancer MDR by iTRAQ-based proteomic analysis

Authors: Xiaojuan Wang, Yani Li, Guanghui Xu, Muhan Liu, Lin Xue, Lijuan Liu, Sijun Hu, Ying Zhang, Yongzhan Nie, Shuhui Liang, Biaoluo Wang, Jie Ding

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Multidrug resistance (MDR) is a major obstacle to the treatment of gastric cancer (GC). Using a phage display approach, we previously obtained the peptide GMBP1, which specifically binds to the surface of MDR gastric cancer cells and is subsequently internalized. Furthermore, GMBP1 was shown to have the potential to reverse the MDR phenotype of gastric cancer cells, and GRP78 was identified as the receptor for this peptide. The present study aimed to investigate the mechanism of peptide GMBP1 and its receptor GRP78 in modulating gastric cancer MDR.

Methods

Fluorescence-activated cell sorting (FACS) and immunofluorescence staining were used to investigate the subcellular location and mechanism of GMBP1 internalization. iTRAQ was used to identify the MDR-associated downstream targets of GMBP1. Differentially expressed proteins were identified in GMBP1-treated compared to untreated SGC7901/ADR and SGC7901/VCR cells. GO and KEGG pathway analyses of the differentially expressed proteins revealed the interconnection of these proteins, the majority of which are involved in MDR. Two differentially expressed proteins were selected and validated by western blotting.

Results

GMBP1 and its receptor GRP78 were found to be localized in the cytoplasm of GC cells, and GRP78 can mediate the internalization of GMBP1 into MDR cells through the transferrin-related pathway. In total, 3,752 and 3,749 proteins were affected in GMBP1-treated SGC7901/ADR and SGC7901/VCR cells, respectively, involving 38 and 79 KEGG pathways. Two differentially expressed proteins, CTBP2 and EIF4E, were selected and validated by western blotting.

Conclusion

This study explored the role and downstream mechanism of GMBP1 in GC MDR, providing insight into the role of endoplasmic reticulum stress protein GRP78 in the MDR of cancer cells.
Appendix
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Metadata
Title
Mechanism study of peptide GMBP1 and its receptor GRP78 in modulating gastric cancer MDR by iTRAQ-based proteomic analysis
Authors
Xiaojuan Wang
Yani Li
Guanghui Xu
Muhan Liu
Lin Xue
Lijuan Liu
Sijun Hu
Ying Zhang
Yongzhan Nie
Shuhui Liang
Biaoluo Wang
Jie Ding
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1361-3

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