MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.
MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.
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MGr1-Ag/37LRP通过FAK/PI3K和MAPK通路诱导胃癌细胞粘附介导的耐药性
DOI：
10.1111/cas.12414
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发表时间：
2014-06
期刊：
影响因子：
5.7
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Sun L;Liu L;Liu X;Wang Y;Li M;Yao L;Yang J;Ji G;Guo C;Pan Y;Liang S;Wang B;Ding J;Zhang H;Shi Y
众所周知，肿瘤微环境在耐药和细胞粘附介导的耐药（CAM-DR）中起着至关重要的作用，CAM-DR是一种新的耐药形式。在我们之前的研究中，我们报道了MGr1-Ag/37LRP结扎诱导的粘附参与保护胃癌细胞免受化疗药物引起的多种凋亡刺激。进一步研究表明MGr1-Ag可能通过与层粘连蛋白相互作用促进CAM-DR。然而，mgr1 - ag启动的细胞内信号转导途径尚不清楚。在本研究中，我们的实验结果表明，胃癌MDR细胞系通过MGr1-Ag与层粘连蛋白相互作用上调Bcl-2介导CAM-DR。进一步研究发现，MGr1-Ag/37LRP作为ECM组分受体，可通过与磷酸化的FAK相互作用激活下游信号通路PI3K/AKT和MAPK/ERK。此外，通过单克隆抗体、siRNA和反义寡核苷酸抑制MGr1-Ag/37LRP的表达可显著提高化疗药物的敏感性。根据这些结果，我们得出FAK/PI3K和MAPK信号通路在mgr1 - ag介导的胃癌CAM-DR中发挥重要作用。MGr1-Ag/37LRP可能是胃癌耐多药逆转的潜在有效靶点。
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.
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影响因子：
5.7
作者：
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