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

Cancer Science

Li Sun²  Lili Liu³  Xiangqiang Liu²  Yafang Wang³  Mengbin Li²  Liping Yao²  Jianjun Yang²  Genlin Ji¹  Changcun Guo²  Yanglin Pan²  Shuhui Liang²  Biaoluo Wang²  Jie Ding²  Hongwei Zhang² 

[1] Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China;State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China;Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China

关键词: CAM‐DR;    FAK/PI3K;    gastric cancer;    MAPK;    MGr1‐Ag/37LRP;   

DOI  :  10.1111/cas.12414

来源: Wiley

【 摘 要 】

Abstract

It is well known that tumor microenvironment plays a vital role in drug resistance and cell adhesion-mediated drug resistance (CAM-DR), a form of de novo drug resistance. In our previous study, we reported that MGr1-Ag/37LRP ligation-induced adhesion participated in protecting gastric cancer cells from a number of apoptotic stimuli caused by chemotherapeutic drugs. Further study suggested that MGr1-Ag could prompt CAM-DR through interaction with laminin. However, the MGr1-Ag-initiated intracellular signal transduction pathway is still unknown. In this study, our experimental results showed that gastric cancer MDR cell lines mediated CAM-DR through upregulation of Bcl-2 by MGr1-Ag interaction with laminin. 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. According to these results, we concluded that the FAK/PI3K and MAPK signal pathway plays an important role in MGr1-Ag-mediated CAM-DR in gastric cancer. MGr1-Ag/37LRP might be a potential effective reversal target to MDR in gastric cancer.

【 授权许可】

CC BY   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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