YB-1 regulates tumor growth by promoting MACC1/c-Met pathway in human lung adenocarcinoma

被引:38
作者
Guo, Tao [1 ,2 ]
Zhao, Shilei [1 ,2 ]
Wang, Peng [1 ,2 ]
Xue, Xiaoyuan [3 ]
Zhang, Yan [4 ]
Yang, Mengying [3 ]
Li, Nan [3 ]
Li, Zhuoshi [1 ,2 ]
Xu, Lingzhi [5 ]
Jiang, Lei [1 ,6 ]
Zhao, Lei [2 ]
Ma, Patrick C. [7 ]
Rosell, Rafael [8 ]
Li, Jinxiu [2 ]
Gu, Chundong [1 ,2 ]
机构
[1] Dalian Med Univ, Dept Thorac Surg, Affiliated Hosp 1, Dalian 116011, Peoples R China
[2] Dalian Med Univ, Affiliated Hosp 1, Lung Canc Diag & Treatment Ctr Dalian, Dalian 116011, Peoples R China
[3] Dalian Med Univ, Inst Canc Stem Cell, Dalian 116044, Peoples R China
[4] Shandong Univ, Dept Radiat Oncol, Qianfoshan Hosp, Jinan 250000, Peoples R China
[5] Dalian Med Univ, Affiliated Hosp 2, Dalian 116011, Peoples R China
[6] Anhui Med Univ, Affiliated Hosp 4, Hefei 230000, Peoples R China
[7] Cleveland Clin, Taussig Canc Inst, Dept Solid Tumor Oncol, Aerodigest Oncol Translat Res THOR, Cleveland, OH 44195 USA
[8] Catalan Inst Oncol, Pangaea Biotech, Dexeus Univ Inst, Breakthrough Canc Res Unit, Badalona 08916, Spain
基金
中国国家自然科学基金;
关键词
YB-1; MACC1; c-Met; lung adenocarcinoma; prognosis; BOX-BINDING PROTEIN-1; CELL-PROLIFERATION; PROGNOSTIC MARKER; POOR-PROGNOSIS; GASTRIC-CANCER; UP-REGULATION; EXPRESSION; MACC1; MET; PREDICTS;
D O I
10.18632/oncotarget.18262
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aberrant overexpression of the transcription/translation factor Y-box-binding protein (YB-1) is associated with poor prognosis of lung adenocarcinoma, however the underlying mechanism by which YB-1 acts has not been fully elucidated. Here, we reported that inhibition of YB-1 diminished proliferation, migration and invasion of lung adenocarcinoma cells. Interestingly, we identified metastasis associated in colon cancer-1 (MACC1) as a target of YB-1. Depletion of YB-1 markedly decreased MACC1 promoter activity and suppressed the MACC1/c-Met signaling pathway in lung adenocarcinoma cells. Additionally, chromatin immunoprecipitation (ChIP) assay demonstrated that YB-1 bound to the MACC1 promoter. Moreover, YB-1 was positively correlated with MACC1, and both proteins were over-expressed in lung adenocarcinoma tissues. The Cox-regression analysis indicated that high YB-1 expression was an independent risk factor for prognosis in enrolled patients. Furthermore, depletion of YB-1 attenuated tumorigenesis in a xenograft mouse model and reduced MACC1 expression in tumor tissues. Collectively, our data suggested that targeting YB-1 suppressed lung adenocarcinoma progression through the MACC1/cMet pathway and that the high expression of YB-1/MACC1 is a potential prognostic marker in lung adenocarcinoma.
引用
收藏
页码:48110 / 48125
页数:16
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