title: Functional cooperation between KCa3.1 and TRPC1 channels in human breast cancer: Role in cell proliferation and patient prognosis.
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.
authors.affiliation: University of Picardie Jules Verne, UFR of Sciences, EA4667 Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France.|Queen's Center for Biomedical Research, The Queen's Medical Center, Honolulu, HI 96813, USA.
authors.forename: Malika
authors.initials: M
authors.lastname: Faouzi
authors.affiliation: University of Picardie Jules Verne, UFR of Sciences, EA4667 Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Hague
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: Geerts
authors.affiliation: University of Picardie Jules Verne, UFR of Sciences, EA4667 Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Ay
authors.affiliation: University of Picardie Jules Verne, UFR of Sciences, EA4667 Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France.|Inserm, UMR1069, Nutrition, Growth and Cancer, University of François Rabelais, Tours F-37032, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Potier-Cartereau
authors.affiliation: University of Picardie Jules Verne, UFR of Sciences, EA4667 Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ahidouch
authors.affiliation: University of Picardie Jules Verne, UFR of Sciences, EA4667 Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France.
authors.forename: Halima
authors.initials: H
authors.lastname: Ouadid-Ahidouch
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D011379:Prognosis; D034622:RNA Interference; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium
keywords: KCa3.1; TRPC1; breast cancer; calcium; cell proliferation