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MGr1-Antigen/37 kDa laminin receptor precursor promotes cellular prion protein induced multi-drug-resistance of gastric cancer

Cellular prion protein (PrP(C)), the infective agent of transmissible spongiform encephalopathies, is thought to be related to several cellular physiological and physiopathological processes. We have previously reported that PrP(C) participates in multi-drug-resistance of gastric cancer. As the sali...

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Detalles Bibliográficos
Autores principales: Luo, Guanhong, Wang, Weijie, Wu, Qiong, Lu, Yuanyuan, Su, Tao, Gu, Nan, Li, Kai, Wang, Jingbo, Du, Rui, Zhao, Xiaodi, Li, Xiaohua, Fan, Rui, Zhang, Hongbo, Nie, Yongzhan, Zhou, Xinmin, Shi, Yongquan, Liang, Jie, Wang, Xin, Fan, Daiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641077/
https://www.ncbi.nlm.nih.gov/pubmed/29069734
http://dx.doi.org/10.18632/oncotarget.17795
Descripción
Sumario:Cellular prion protein (PrP(C)), the infective agent of transmissible spongiform encephalopathies, is thought to be related to several cellular physiological and physiopathological processes. We have previously reported that PrP(C) participates in multi-drug-resistance of gastric cancer. As the salient ligand molecule of PrP for participating in internalization and propagation of the scrapie form of prion protein (PrP(Sc)), 37 kDa laminin receptor precursor protein (37LRP) shared the same gene coding sequence of MGr1-Ag, another protein previously found to be involved in multi-drug-resistance of gastric cancer in our lab. In the present study, we explored whether MGr1-Ag/37LRP contributed to PrP(C) mediated multi-drug-resistance in gastric cancer. Immunohistochemical staining showed similar expression patterns of MGr1-Ag/37LRP and PrP(C) in gastric cancer tissue serial sections. Western blot and immunohistochemistry also demonstrated correlative expression of MGr1-Ag/37LRP and PrP(C) in gastric cancer cell lines. Interaction between MGr1-Ag/37LRP and PrP(C) in gastric cancer cell lines and gastric cancer tissues were verified by immunofluorescence and co-immunoprecipitation. Furthermore, knockdown of MGr1-Ag/37LRP significantly attenuated PrP(C) induced multi-drug-resistance by sensitizing drug-induced apoptosis through inhibition of AKT activation. In conclusion, MGr1-Ag/37LRP may interact with PrP(C) and promote the PrP(C) induced multi-drug-resistance in gastric cancer through PI3K/AKT pathway. The current study elucidates the mechanism of how PrP(C) triggers intracellular signaling cascade resulting in multi-drug-resistance phenotype and provides a novel candidate molecular target against gastric cancer.