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Direct inhibition of TRPC3 by polyunsaturated fatty acids in MCF‐7 breast cancer cells
Author(s) -
Gu Yuchun,
To Wilson,
KirkmanBrown Jackson,
Zhang Jin,
Potier Marie,
Vandier Christophe,
Kumar Prem
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a329-c
Subject(s) - trpc , transient receptor potential channel , trpc5 , trpc3 , trpv , polyunsaturated fatty acid , arachidonic acid , chemistry , microbiology and biotechnology , cancer cell , trpm2 , trpc1 , biochemistry , unsaturated fatty acid , biology , receptor , fatty acid , cancer , enzyme , genetics , trpv1
Transient receptor potential (TRP) channels are a diverse and widely expressed family of cation‐permeable ion channels with mammalian homologues of the Drosophila TRP gene encoding for at least 20 channel proteins including members of the TRPC, V, N, M, P and ML sub‐families. These channels mediate transmembrane Ca 2+ entry in response to a variety of physico‐chemical stimuli including temperature, stretch, redox and so‐called, store depletion as well as G‐protein coupled receptor activation. Polyunsaturated fatty acids (PUFA), including arachidonic acid and linolenic acid, are known to activate Drosophila TRP and TRP‐like, as well as mammalian TRPV channels and mediate calcium entry through an undefined mechanism. Using Ca 2+ imaging and patch clamping, we have shown that polyunsaturated fatty acids interact directly with TRPC3 channels in human MCF‐7 breast cancer cells and act to inhibit capacitative Ca 2+ conductance. Inhibition of TRPC further selectively reduced the S phase of the MCF‐7 cell cycle and cell migration, suggesting a functional role for TRP‐mediated Ca 2+ entry in DNA synthesis and replication in proliferating cancer cells and invasion. We propose that Ca 2+ entry through TRPC channels is regulated by the balance between the metabolic production and degradation of intracellular PUFA and only when disinhibited can the channel be activated by other stimuli, possibly suggesting a mechanism by which PUFA might act in breast cancer. This work was supported by The BBSRC