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.
Keywords: TRPP2; eukaryotic translation initiation factor; human laryngeal squamous cell carcinoma; proliferation; protein kinase R-like endoplasmic reticulum kinase; tumor necrosis factor α.