Critical role of TRPC6 channels in G2 phase transition and the development of human oesophageal cancer.
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 Ca(2+) 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 Ca(2+) concentration ([Ca(2+)](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.


CONCLUSIONS
TRPC6 channels play a critical role in the development of OSCC. The [Ca(2+)](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.
Shi
Y
Y
Department of Thoracic Surgery, ZhongShan Hospital and Shanghai Medical School, Fudan University, Shanghai, China.
Ding
X
X
He
Z-H
ZH
Zhou
K-C
KC
Wang
Q
Q
Wang
Y-Z
YZ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004938:Esophageal Neoplasms / Q000209:etiology / Q000378:metabolism*; D016195:G2 Phase / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D000074287:TRPC6 Cation Channel
D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human