Open AccessMG r1‐Ag/37 LRP induces cell adhesion‐mediated drug resistance through FAK / PI 3K and MAPK pathway in gastric cancer
Author(s) -
Sun Li,
Liu Lili,
Liu Xiangqiang,
Wang Yafang,
Li Mengbin,
Yao Liping,
Yang Jianjun,
Ji Genlin,
Guo Changcun,
Pan Yanglin,
Liang Shuhui,
Wang Biaoluo,
Ding Jie,
Zhang Hongwei,
Shi Yongquan
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12414
Subject(s) - mapk/erk pathway , pi3k/akt/mtor pathway , cancer cell , protein kinase b , cancer , signal transduction , cancer research , chemistry , cell adhesion , microbiology and biotechnology , pharmacology , cell , medicine , biology , biochemistry
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 mA bs, 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.