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Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells

Oncogene volume 33, pages 1239–1248 (2014)Cite this article

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Abstract

Smoking is the most important risk factor for both lung cancer (LC) and chronic obstructive pulmonary disease. The aim of this study was to investigate the role of myeloid cell nuclear factor-κB in the regulation of tumor cell growth signaling. We subjected mice lacking myeloid RelA/p65 (relaΔ−/−) to a metastatic LC model. Cigarette smoke (CS) exposure significantly increased the proliferation of Lewis lung carcinoma cell tumors in wild-type mice. In CS-exposed relaΔ−/− mice, the tumor growth was largely inhibited. Transcriptome and pathway analysis of cancer tissue revealed a fundamental impact of myeloid cells on various growth signaling pathways, including the Wnt/β-catenin pathway. In conclusion, myeloid RelA/p65 is necessary to link smoke-induced inflammation with LC growth and has a role in the activation of Wnt/β-catenin signaling in tumor cells.

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Acknowledgements

This work was supported by Grants of the Deutsche Forschungsgemeinschaft (DFG Ba 1641/12), the Federal Ministry of Education and Research (FKZ 01GI0881-0888), and the LOEWE-Schwerpunkt ‘Tumor and Inflammation’ of the state of Hesse to RB. We thank Thomas Damm, Andreas Kamyschnikow and Anja Honecker for excellent technical support. We thank Professor Ingrid Förster for making the LysMcre animal available for this study.

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Author notes

  1. D Li

    Present address: 7Current address: Department of Clinical Laboratory, Tongji Hospital of Tongji University, 200065, Shanghai, China.,

Authors and Affiliations

  1. Department of Internal Medicine V—Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany

    D Li, C Beisswenger, C Herr, J Hellberg, G Han, T Zakharkina, M Voss & R Bals

  2. Pulmonary Division, Department of Medicine A, Münster University Hospital, Münster, Germany

    R Wiewrodt

  3. Department of Pathology, Saarland University Hospital, Homburg, Germany

    R M Bohle

  4. Institute for Clinical and Experimental Surgery, Saarland University, Homburg, Germany

    M D Menger

  5. Department of Internal Medicine II, Technical University of Munich, Munich, Germany

    R M Schmid

  6. Center for Bioinformatics, Saarland University, Saarbrücken, Germany

    D Stöckel & H-P Lenhof

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Correspondence to R Bals.

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Li, D., Beisswenger, C., Herr, C. et al. Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells. Oncogene 33, 1239–1248 (2014). https://doi.org/10.1038/onc.2013.75

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