MGr1-Antigen/37 kDa laminin receptor precursor promotes cellular prion protein induced multi-drug-resistance of gastric cancer.
MGr1-Antigen/37 kDa laminin receptor precursor promotes cellular prion protein induced multi-drug-resistance of gastric cancer.
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MGr1-Antigen/37 kDa层粘连蛋白受体前体促进细胞朊病毒蛋白诱导的胃癌多重耐药
DOI：
10.18632/oncotarget.17795
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发表时间：
2017-09-22
期刊：
影响因子：
--
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Luo G;Wang W;Wu Q;Lu Y;Su T;Gu N;Li K;Wang J;Du R;Zhao X;Li X;Fan R;Zhang H;Nie Y;Zhou X;Shi Y;Liang J;Wang X;Fan D
细胞朊病毒蛋白（PrPC）是传染性海绵状脑病的感染因子，被认为与多种细胞生理和病理生理过程有关。我们以前报道过PrPC参与胃癌的多药耐药。37 kDa层粘连蛋白受体前体蛋白（37LRP）作为PrP参与痒病型朊蛋白（PrPSc）内化繁殖的显著配体分子，与本实验室先前发现的另一种参与胃癌多重耐药的蛋白MGr1-Ag具有相同的基因编码序列。在本研究中，我们探讨MGr1-Ag/37LRP是否参与了PrPC介导的胃癌多药耐药。免疫组化染色显示MGr1-Ag/37LRP和PrPC在胃癌组织序列切片中的表达模式相似。Western blot和免疫组化也证实MGr1-Ag/37LRP和PrPC在胃癌细胞系中有相关表达。采用免疫荧光法和共免疫沉淀法验证胃癌细胞系和胃癌组织中MGr1-Ag/37LRP与PrPC的相互作用。此外，敲低MGr1-Ag/37LRP可通过抑制AKT活化使药物诱导的细胞凋亡增敏，从而显著减弱PrPC诱导的多药耐药。综上所述，MGr1-Ag/37LRP可能通过PI3K/AKT通路与PrPC相互作用，促进PrPC诱导的胃癌多药耐药。本研究阐明了PrPC触发细胞内信号级联导致多药耐药表型的机制，为胃癌提供了新的候选分子靶点。
Cellular prion protein (PrPC), the infective agent of transmissible spongiform encephalopathies, is thought to be related to several cellular physiological and physiopathological processes. We have previously reported that PrPC 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 (PrPSc), 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 PrPC mediated multi-drug-resistance in gastric cancer. Immunohistochemical staining showed similar expression patterns of MGr1-Ag/37LRP and PrPC in gastric cancer tissue serial sections. Western blot and immunohistochemistry also demonstrated correlative expression of MGr1-Ag/37LRP and PrPC in gastric cancer cell lines. Interaction between MGr1-Ag/37LRP and PrPC in gastric cancer cell lines and gastric cancer tissues were verified by immunofluorescence and co-immunoprecipitation. Furthermore, knockdown of MGr1-Ag/37LRP significantly attenuated PrPC induced multi-drug-resistance by sensitizing drug-induced apoptosis through inhibition of AKT activation. In conclusion, MGr1-Ag/37LRP may interact with PrPC and promote the PrPC induced multi-drug-resistance in gastric cancer through PI3K/AKT pathway. The current study elucidates the mechanism of how PrPC triggers intracellular signaling cascade resulting in multi-drug-resistance phenotype and provides a novel candidate molecular target against gastric cancer.
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影响因子：
4.8
作者：
Liang, Jie;Pan, Yanglin;Fan, Daiming
通讯作者：
Fan, Daiming
影响因子：
4.8
作者：
Pan, Yanglin;Zhao, Lina;Fan, Daiming
通讯作者：
Fan, Daiming
影响因子：
6.4
作者：
Du, JP;Pan, YL;Fan, DM
通讯作者：
Fan, DM
影响因子：
--
作者：
Liang, J;Pan, YL;Fan, DM
通讯作者：
Fan, DM
影响因子：
3.6
作者：
Liang, Jie;Bai, Feihu;Fan, Daiming
通讯作者：
Fan, Daiming