Oncotarget

Research Papers:

Functional cooperation between KCa3.1 and TRPC1 channels in human breast cancer: Role in cell proliferation and patient prognosis

Malika Faouzi, Frederic Hague, Dirk Geerts, Anne-Sophie Ay, Marie Potier-Cartereau, Ahmed Ahidouch and Halima Ouadid-Ahidouch _

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Oncotarget. 2016; 7:36419-36435. https://doi.org/10.18632/oncotarget.9261

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Abstract

Malika Faouzi1,2, Frederic Hague1, Dirk Geerts3, Anne-Sophie Ay1, Marie Potier-Cartereau1,4, Ahmed Ahidouch1, Halima Ouadid-Ahidouch1

1University of Picardie Jules Verne, UFR of Sciences, EA4667 Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France

2Queen’s Center for Biomedical Research, The Queen’s Medical Center, Honolulu, HI 96813, USA

3Department of Pediatric Oncology/Hematology, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands

4Inserm, UMR1069, Nutrition, Growth and Cancer, University of François Rabelais, Tours F-37032, France

Correspondence to:

Halima Ouadid-Ahidouch, email: [email protected]

Malika Faouzi, email: [email protected]

Keywords: breast cancer, cell proliferation, calcium, KCa3.1, TRPC1

Received: October 14, 2015     Accepted: April 08, 2016     Published: May 10, 2016

ABSTRACT

Intracellular Ca2+ levels are important regulators of cell cycle and proliferation. We, and others, have previously reported the role of KCa3.1 (KCNN4) channels in regulating the membrane potential and the Ca2+ entry in association with cell proliferation. However, the relevance of KC3.1 channels in cancer prognosis as well as the molecular mechanism of Ca2+ entry triggered by their activation remain undetermined. Here, we show that RNAi-mediated knockdown of KCa3.1 and/or TRPC1 leads to a significant decrease in cell proliferation due to cell cycle arrest in the G1 phase. These results are consistent with the observed upregulation of both channels in synchronized cells at the end of G1 phase. Additionally, knockdown of TRPC1 suppressed the Ca2+ entry induced by 1-EBIO-mediated KCa3.1 activation, suggesting a functional cooperation between TRPC1 and KCa3.1 in the regulation of Ca2+ entry, possibly within lipid raft microdomains where these two channels seem to co-localize. We also show significant correlations between KCa3.1 mRNA expression and poor patient prognosis and unfavorable clinical breast cancer parameters by mining large datasets in the public domain. Together, these results highlight the importance of KCa3.1 in regulating the proliferative mechanisms in breast cancer cells as well as in providing a promising novel target in prognosis and therapy.


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