YB-1 regulates tumor growth by promoting MACC1/c-Met pathway in human lung adenocarcinoma
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Tao Guo1,2,*, Shilei Zhao1,2,*, Peng Wang1,2,*, Xiaoyuan Xue3, Yan Zhang4, Mengying Yang3, Nan Li3, Zhuoshi Li1,2, Lingzhi Xu5, Lei Jiang6, Lei Zhao1,2, Patrick C. Ma7, Rafael Rosell8, Jinxiu Li2 and Chundong Gu1,2
1Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
2Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
3Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China
4Department of Radiation Oncology, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250000, China
5The Second Affiliated Hospital, Dalian Medical University, Dalian 116011, China
6The Fourth Affiliated Hospital, Anhui Medical University, Hefei 230000, China
7Aerodigestive Oncology Translational Research THOR, Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA
8Breakthrough Cancer Research Unit, Pangaea Biotech, Dexeus University Institute, Catalan Institute of Oncology, Badalona 08916, Spain
Written on behalf of the AME Thoracic Surgery Collaborative Group
*These authors have contributed equally to this work
Chundong Gu, email: email@example.com
Jinxiu Li, email: lijinxiu@ dmu.edu.cn
Keywords: YB-1, MACC1, c-Met, lung adenocarcinoma, prognosis
Abbreviations: YB-1: Y-box-binding protein-1; MACC1: metastasis associated in colon cancer-1; NSCLC: non-small-cell lung cancer; ChIP: chromatin immunoprecipitation; IHC: immunohistochemistry
Received: January 18, 2017 Accepted: May 03, 2017 Published: May 29, 2017
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/c-Met pathway and that the high expression of YB-1/MACC1 is a potential prognostic marker in lung adenocarcinoma.
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