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Critical role of TRPC6 channels in G2 phase transition and the development of human oesophageal cancer
  1. Y Shi1,
  2. X Ding2,3,
  3. Z-H He2,3,
  4. K-C Zhou2,3,
  5. Q Wang1,
  6. Y-Z Wang2
  1. 1
    Department of Thoracic Surgery, ZhongShan Hospital and Shanghai Medical School, Fudan University, Shanghai, China
  2. 2
    Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institute for Biological Sciences, State Key Laboratory of Neuroscience, Shanghai, China
  3. 3
    The Graduate School, Chinese Academy of Sciences, Shanghai, China
  1. Correspondence to Dr Y Wang, Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institute for Biological Sciences, State Key Laboratory of Neuroscience, Shanghai, China; yzwang{at}ion.ac.cn, or to Dr Q Wang, Department of Thoracic Surgery, ZhongShan Hospital and Shanghai Medical School, Fudan University, Shanghai, China; doctorwangqun{at}yahoo.com.cn

Abstract

Background: Oesophageal squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related death worldwide. However, the mechanism by which the OSCC 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 OSCC development is unknown.

Methods: The expression of TRPC6, a member of TRPC subfamily, was examined in samples from patients with OSCC by immunostaining and in situ hybridisation. The effects of TRPC6 channels on OSCC cell cycle progression, cell growth and in vivo tumour formation were investigated. The functional TRPC6 channels were found in OSCC cells by electrophysiology and Ca2+ imaging analysis.

Results: The expression of TRPC6 at protein and mRNA levels was markedly increased in human OSCC specimens than that in normal human oesophageal tissues. Blockade of TRPC6 channels in human OSCC cells inhibited elevation of intracellular Ca2+ concentration ([Ca2+]i) and activation of Cdc2 kinase. Meanwhile, the OSCC cell cycle was arrested at G2 phase and the cell growth was suppressed. Furthermore, inhibition of TRPC6 channels suppressed in nude mice the tumour formation generated by injection of the OSCC cells.

Conclusion: TRPC6 channels play a critical role in the development of OSCC. The [Ca2+]i elevation regulated by TRPC6 channels is essential for G2 phase progression and OSCC development. These channels might be a novel target for therapeutic intervention of OSCC.

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Footnotes

  • Funding This work was supported by grants from the 973 Program (2006CB806600) and projects 30711120566 and U0632006 from the National Natural Science Foundation of China and B116 from Shanghai Leading Academic Discipline Project.

  • Competing interests None.

  • Provenance and Peer review Not commissioned; externally peer reviewed.

  • Ethics approval Approval for the use of clinical specimens was given by ZhongShan Hospital Research Ethics Committee. The animal welfare guidelines of the Institute of Neuroscience, CAS were followed and the experimental protocol was approved by the Animal Care Committee, ION.

  • ▸ Supplementary methods, tables and figures are published online only at http://gut.bmj.com/content/vol58/issue11

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