Abstract
TRPP2, a Ca2+-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine extensively involved in immune system regulation, cell proliferation and cell survival. However, the effects and mechanisms for the role of TNF-α in laryngeal cancer remain unclear. Here, we demonstrated using western blot analyses and intracellular Ca2+ concentration measurements that TNF-α treatment suppressed both TRPP2 expression and ATP-induced Ca2+ release in a laryngeal cancer cell line (Hep-2). Knockdown of TRPP2 by a specific siRNA significantly decreased ATP-induced Ca2+ release and abolished the effect of TNF-α on the ATP-induced Ca2+ release. TNF-α treatment also enhanced Hep-2 cell proliferation and growth, as determined using cell counting and flow cytometry cell cycle assays. Moreover, TNF-α treatment down-regulated phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK) and phosphorylated eukaryotic translation initiation factor (p-eIF2α) expression levels, without affecting PERK and eIF2α expression levels in Hep-2 cells. We concluded that suppressing TRPP2 expression and TRPP2-mediated Ca2+ signaling may be one mechanism underlying TNF-α-enhanced Hep-2 cell proliferation. These results offer new insights into the mechanisms of TNF-α-mediated laryngeal cancer cell proliferation, and provide evidences showing a potential role of TNF-α in the development of laryngeal cancer.
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Acknowledgements
This work was supported by the Anhui Provincial Natural Science Foundation (1408085MH157), Supporting Program for Excellent Young Talents in Universities of Anhui Province, Outstanding Young Investigator of Anhui Medical University, National Natural Science Foundation of China (81570403, 81371284), and Scientific Research Grant of Anhui Medical University (2015xkj080).
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Wu, J., Guo, J., Yang, Y. et al. Tumor necrosis factor α accelerates Hep-2 cells proliferation by suppressing TRPP2 expression. Sci. China Life Sci. 60, 1251–1259 (2017). https://doi.org/10.1007/s11427-016-9030-5
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DOI: https://doi.org/10.1007/s11427-016-9030-5