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

// Guanhong Luo 1, * , Weijie Wang 1, * , Qiong Wu 1, * , Yuanyuan Lu 1, * , Tao Su 2 , Nan Gu 3 , Kai Li 1 , Jingbo Wang 1 , Rui Du 4 , Xiaodi Zhao 1 , Xiaohua Li 1 , Rui Fan 1 , Hongbo Zhang 1 , Yongzhan Nie 1 , Xinmin Zhou 1 , Yongquan Shi 1 , Jie Liang 1 , Xin Wang 1 and Daiming Fan 1 1 State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China 2 Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China 3 Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China 4 Department of Radiotherapy Oncology, Navy General Hospital, Beijing, China * These authors contributed equally to this work Correspondence to: Jie Liang, email: liangjie@fmmu.edu.cn Xin Wang, email: wangxinpaper@163.com Daiming Fan, email: fandaim@fmmu.edu.cn Keywords: PrP C , MGr1-Ag/37LRP, gastric cancer, multi-drug-resistance (MDR), apoptosis Received: August 02, 2016      Accepted: April 24, 2017      Published: May 11, 2017 ABSTRACT 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 PrPC 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.