Abstract
Metabolism alteration is one of the hallmarks of cancer cells. Although several studies have demonstrated that glycolysis played important roles in the progression of nasopharyngeal carcinoma (NPC), the functions of specific metabolism-associated genes remain largely unknown. In this study, it was found that Pyruvate dehydrogenase B (PDHB), which catalyzed the conversion of pyruvate to Acetyl-CoA, was downregulated in NPC cells. Forced expression of PDHB in NPC cells inhibited cell growth and migration, while knocking down the expression of PDHB promoted the growth, migration, and tumorigenesis of NPC cells. Mechanism study showed that PDHB inhibited ERK signaling and cell growth driven by RasV12. Collectively, our study demonstrated the suppressive roles of PDHB in the progression of NPC, and restoring the function of PDHB might be a promising strategy for NPC therapy.
Similar content being viewed by others
References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.
Lourembam DS et al. Evaluation of risk factors for nasopharyngeal carcinoma in a high-risk area of India, the northeastern region. Asian Pac J Cancer Prev. 2015;16(12):4927–35.
Isobe K et al. Advanced nasopharyngeal carcinoma treated with chemotherapy and radiotherapy: distant metastasis and local recurrence. Int J Oncol. 1998;12(5):1183–7.
Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell. 2008;134(5):703–7.
Saunier E, Benelli C, Bortoli S. The pyruvate dehydrogenase complex in cancer: an old metabolic gatekeeper regulated by new pathways and pharmacological agents. Int J Cancer. 2015;138:809–17.
Kerbey AL, Richardson LJ, Randle PJ. The roles of intrinsic kinase and of kinase/activator protein in the enhanced phosphorylation of pyruvate dehydrogenase complex in starvation. FEBS Lett. 1984;176(1):115–9.
Goh WQ et al. DLAT subunit of the pyruvate dehydrogenase complex is upregulated in gastric cancer-implications in cancer therapy. Am J Transl Res. 2015;7(6):1140–51.
Sun XR et al. Expression of pyruvate dehydrogenase is an independent prognostic marker in gastric cancer. World J Gastroenterol. 2015;21(17):5336–44.
Cai Z et al. A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism. Mol Cell Proteomics. 2010;9(12):2617–28.
Zuo Q et al. The Ras signaling pathway mediates cetuximab resistance in nasopharyngeal carcinoma. Biomed Pharmacother. 2011;65(3):168–74.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.
Lo AK et al. Activation of the FGFR1 signalling pathway by the Epstein-Barr virus-encoded LMP1 promotes aerobic glycolysis and transformation of human nasopharyngeal epithelial cells. J Pathol. 2015. doi:10.1002/path.4575.
Xiao L et al. Targeting Epstein-Barr virus oncoprotein LMP1-mediated glycolysis sensitizes nasopharyngeal carcinoma to radiation therapy. Oncogene. 2014;33(37):4568–78.
Lan YY et al. Epstein-Barr virus latent membrane protein 2A promotes invasion of nasopharyngeal carcinoma cells through ERK/Fra-1-mediated induction of matrix metalloproteinase 9. J Virol. 2012;86(12):6656–67.
Peng C et al. BRD7 suppresses the growth of nasopharyngeal carcinoma cells (HNE1) through negatively regulating beta-catenin and ERK pathways. Mol Cell Biochem. 2007;303(1–2):141–9.
Li YJ et al. Dasatinib suppresses invasion and induces apoptosis in nasopharyngeal carcinoma. Int J Clin Exp Pathol. 2015;8(7):7818–24.
Acknowledgments
This work was supported by the grants of Chen T. from the Medical Research Foundation of Guangdong Provincial Health and Family Planning Commission (A2015005), the National Natural Science Foundation of China (81402963), and the First Affiliated Hospital of Guangzhou Medical University (the “Young Elite Talents Program” and the “Science and Technology Support Projects”).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
All procedures performed in this study involving mouse were in accordance with the ethical standards of the hospital.
Conflicts of interest
None
Additional information
Hongbo Tang, Xinggu Luo, Juan Li and Yi Zhou contributed equally to this work.
Rights and permissions
About this article
Cite this article
Tang, H., Luo, X., Li, J. et al. Pyruvate dehydrogenase B promoted the growth and migration of the nasopharyngeal carcinoma cells. Tumor Biol. 37, 10563–10569 (2016). https://doi.org/10.1007/s13277-016-4922-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-016-4922-4