Discoidin domain receptor 1 promotes lung adenocarcinoma migration via the AKT/snail signaling axis
Discoidin domain receptor 1 promotes lung adenocarcinoma migration via the AKT/snail signaling axis
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Discoidin 结构域受体 1 通过 AKT/snail 信号轴促进肺腺癌迁移
DOI：
10.1007/s11033-022-07509-8
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发表时间：
2022-05
影响因子：
2.8
通讯作者：
Jianxin Lyu
中科院分区：
文献类型：
--
作者：
Jingjing Zhu;Huang Cheng;Lan Wang;Weide Xu;Junqing Wang;Qing Han;Jong-Ho Lee;Linyong Du;Jianxin Lyu
盘状结构域受体1（DDR 1）是受体酪氨酸激酶的成员，与肿瘤的进展有关。然而，DDR 1在肺腺癌（LUAD）进展中的功能和潜在机制尚不清楚。因此，本研究通过Transwell实验、创伤愈合实验和异种移植瘤实验研究DDR 1在LUAD发生发展过程中的作用，探讨DDR 1在LUAD迁移中的分子调控机制。采用免疫印迹和实时定量聚合酶链反应（RT-qPCR）检测基因表达水平。进行免疫共沉淀（co-IP）测定以检测DDR 1和AKT之间的相互作用。结果LUAD组织中DDR 1的表达明显高于正常肺组织，且DDR 1的表达水平与LUAD患者的预后呈负相关。我们发现DDR 1在体外促进LUAD细胞的迁移和侵袭。此外，LUAD细胞中DDR 1的异位表达改变了EMT相关标志物的表达。重要的是，DDR 1蛋白与AKT和磷酸化AKT相互作用。AKT抑制剂MK 2206中断了DDR 1过表达LUAD细胞中Snail的上调。最后，我们的研究发现，在肿瘤异种移植小鼠模型中，DDR 1的缺失减弱了LUAD细胞的迁移，我们的研究发现，高丰度的DDR 1通过AKT/Snail信号轴增加了LUAD细胞的迁移和侵袭能力，这表明DDR 1可能是治疗LUAD的潜在靶点。
Discoidin domain receptor 1 (DDR1), a member of receptor tyrosine kinase, has been implicated in tumor progression. However, the function and underlying mechanism of DDR1 in lung adenocarcinoma (LUAD) progression is unclear. Thus, we explored the molecular regulatory mechanism of DDR1 in the migration of LUAD.Transwell assays, wound healing assays and xenograft tumor assays were performed to study the function of DDR1 in the progression of LUAD. Immunoblotting and quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression levels of genes. Co-immunoprecipitation (co-IP) assays were performed to detect the interaction between DDR1 and AKT. Immunofluorescence and immunohistochemistry assays were used to determine the expression level of proteins in cells and tissues, respectively.DDR1 expression was significantly higher in LUAD tissues than in normal lung tissues, and the level of DDR1 was inversely correlated with prognosis in patients. We found that DDR1 promoted the migration and invasion of LUAD cells in vitro. Furthermore, ectopic expression of DDR1 in LUAD cells altered EMT-related markers expression. Importantly, the DDR1 protein interacted with AKT and phosphorylated AKT. The AKT inhibitor MK2206 interrupted Snail upregulation in DDR1-overexpressing LUAD cells. Finally, our study revealed that depletion of DDR1 attenuated LUAD cell migration in a tumor xenograft mouse model.Our findings uncovered that a high abundance of DDR1 increased the migration and invasion capability of LUAD cells via the AKT/Snail signaling axis and indicated that DDR1 could be a potential target for treating LUAD.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
7.4
作者：
Kethiwale, Sandeepkumar;Borza, Corina M.;Lowe, Edward W., Jr.;Pozzi, Ambra;Meiler, Jens
通讯作者：
Meiler, Jens
DOI：
10.1097/jto.0b013e31826df166
发表时间：
2012-12
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
J. Riess;J. Neal
通讯作者：
J. Riess;J. Neal
影响因子：
11.2
作者：
Guo G;Gong K;Wohlfeld B;Hatanpaa KJ;Zhao D;Habib AA
通讯作者：
Habib AA
影响因子：
13.3
作者：
Vehlow, Anne;Cordes, Nils
通讯作者：
Cordes, Nils