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

Tao Guo, Shilei Zhao, Peng Wang, Xiaoyuan Xue, Yan Zhang, Mengying Yang, Nan Li, Zhuoshi Li, Lingzhi Xu, Lei Jiang, Lei Zhao, Patrick C. Ma, Rafael Rosell, Jinxiu Li, Chundong Gu

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)48110-48125
Number of pages16
JournalOncotarget
Volume8
Issue number29
DOIs
StatePublished - 2017

All Science Journal Classification (ASJC) codes

  • Oncology

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    Guo, T., Zhao, S., Wang, P., Xue, X., Zhang, Y., Yang, M., Li, N., Li, Z., Xu, L., Jiang, L., Zhao, L., Ma, P. C., Rosell, R., Li, J., & Gu, C. (2017). YB-1 regulates tumor growth by promoting MACC1/c-Met pathway in human lung adenocarcinoma. Oncotarget, 8(29), 48110-48125. https://doi.org/10.18632/oncotarget.18262