Background: Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related death worldwide. However, the mechanism by which the ESCC develops remains largely unknown. Ion channels are important for cancer development. Whether the transient receptor potential canonical (TRPC), known as the non-selective cation channels, plays a role in ESCC development is unknown.
Methods: The expression of TRPC6, a member of TRPC subfamily, was examined in ESCC patient samples by immunostaining and in situ hybridization. The effects of TRPC6 channels on ESCC cell cycle progression, cell growth and in vivo tumor formation were investigated. The functional TRPC6 channels were found in ESCC cells by electrophysiology and Ca2+ imaging analysis.
Results: The expression of TRPC6 at protein and mRNA levels was markedly increased in human ESCC specimens than that in normal human esophageal tissues. Blockade of TRPC6 channels in human ESCC cells inhibited elevation of intracellular Ca2+ concentration ([Ca2+]i) and activation of Cdc2 kinase. Meanwhile, the ESCC cell cycle was arrested at G2 phase and the cell growth was suppressed. Furthermore, inhibition of TRPC6 channels suppressed in nude mice the tumor formation generated by injection of the ESCC cells.
Conclusion: TRPC6 channels play a critical role in the development of ESCC. The [Ca2+]i elevation regulated by TRPC6 channels is essential for G2 phase progression and ESCC development. These channels might be a novel target for therapeutic intervention of ESCC.
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