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TRAF6 is required for BLyS-mediated NF-κB signaling in multiple myeloma cells

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Abstract

Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals from members of the IL-1R/TLR and TNFR superfamilies to the transcription factors NF-κB and AP1. Elevated expression of the TNF family member B-lymphocyte stimulator (BLyS) in multiple myeloma (MM) has been described recently. However, the precise process by which BLyS signals in myeloma cell remains unknown. Here, we identified increased expression of TRAF6 in MM patient cells and the MM cell lines U266, RPMI8226, and KM3. Furthermore, rhBLyS induced TRAF6 up-regulation in these cells in a dose-dependent manner. Both the classical and alternative NF-κB pathways were activated by rhBLyS treatment. Depletion of TRAF6 by siRNA decreased levels of p-p65 and p-p100, even after stimulation with rhBLyS. Down-regulation of TRAF6 also abrogated rhBLyS-mediated cell viability. These findings suggest that TRAF6 is required for BLyS-mediated NF-κB signaling in myeloma cells and is a potential molecular therapeutic target in MM.

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Acknowledgments

Thanks for technical help from Ju Shaoqing, Ph.D., of Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University.

Funding source

This work was supported by the National Youth Science Foundation (81201857) and the Natural Science Foundation of Jiangsu Province, China (BK2011388).

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Authors and Affiliations

  1. Affiliated Hospital of Nantong University, Department of Hematology, Nantong, 226001, Jiangsu, China

    Xinfeng Wang, Jingjing Wang, Hong Liu, Ruirong Xu, Runsheng Ding, Shenhua Jiang & Hongming Huang

  2. Center of Clinical Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Xudong Wang

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  1. Xinfeng Wang
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  2. Jingjing Wang
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  3. Hong Liu
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  4. Ruirong Xu
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  5. Runsheng Ding
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  6. Shenhua Jiang
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  7. Xudong Wang
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  8. Hongming Huang
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Correspondence to Xudong Wang or Hongming Huang.

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Xinfeng Wang and Jingjing Wang are co-first authors.

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Wang, X., Wang, J., Liu, H. et al. TRAF6 is required for BLyS-mediated NF-κB signaling in multiple myeloma cells. Med Oncol 32, 239 (2015). https://doi.org/10.1007/s12032-015-0671-2

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  • DOI: https://doi.org/10.1007/s12032-015-0671-2

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