Up-regulation of Kv7.1 channels in thromboxane A2-induced colonic cancer cell proliferation

Takahiro Shimizu, Takuto Fujii, Yuji Takahashi, Yuta Takahashi, Tomoyuki Suzuki, Masashi Ukai, Katsunori Tauchi, Naoki Horikawa, Kazuhiro Tsukada, Hideki Sakai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Thromboxane A2 (TXA2) is known to stimulate colonic cancer cell proliferation, although the mechanism has not been clarified. In this study, we compared the expression levels of Kv7.1 K+ channels between human colorectal cancer tissue and the accompanying non-tumor mucosa. Kv7.1 proteins were found to be consistently up-regulated in the cancer tissues from different patients. Kv7.1 was also expressed in human colonic cancer cell lines. Treatment of colonic cancer cells with 9,11-epithio-11,12-methano- thromboxane A2 (STA2), a stable analogue of TXA 2, significantly increased whole-cell K+ currents sensitive to chromanol 293B, an inhibitor of Kv7.1 channels, in parallel with an increased expression of Kv7.1 proteins. In contrast, TXB2, an inactive metabolite of TXA2, had no effects on expression level and function of Kv7.1. A TXA2 receptor antagonist (SQ29548) and an inhibitor of cAMP-dependent protein kinase (Rp-8-Br-MB-cAMPS) inhibited STA 2-induced increases in both Kv7.1 expression and chromanol 293B-sensitive K+ currents. Interestingly, STA2-stimulated proliferation of colonic cancer cells was inhibited by chromanol 293B. These results suggest that Kv7.1 channels are involved in the TXA2-induced cancer cell proliferation and that they are up-regulated by the TXA2 receptor-mediated cAMP pathway.

Original languageEnglish
Pages (from-to)541-548
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume466
Issue number3
DOIs
StatePublished - 2014/03

Keywords

  • Cancer
  • Colon
  • K channel
  • Kv7.1
  • Proliferation
  • Thromboxane

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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