Abstract
Na(V)1.5 sodium channels enhance the invasiveness of breast cancer cells through the acidic-dependent activation of cysteine cathepsins. Here, we showed that the Na(+)/H(+) exchanger type 1 (NHE1) was an important regulator of H(+) efflux in breast cancer cells MDA-MB-231 and that its activity was increased by Na(V)1.5. Na(V)1.5 and NHE1 were colocalized in membrane rafts containing caveolin-1. The inhibition of Na(V)1.5 or NHE1 induced a similar reduction in cell invasiveness and extracellular matrix degradation; no additive effect was observed when they were simultaneously inhibited. Our study suggests that Na(V)1.5 and NHE1 are functionally coupled and enhance the invasiveness of cancer cells by increasing H(+) efflux.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Biological Transport
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Breast Neoplasms / pathology*
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism*
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Caveolae / metabolism*
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Cell Line, Tumor
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Humans
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Hydrogen-Ion Concentration
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Intracellular Space / chemistry
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Intracellular Space / metabolism
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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NAV1.5 Voltage-Gated Sodium Channel
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Neoplasm Invasiveness
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Protein Transport
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Protons*
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Sodium Channels / genetics
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Sodium Channels / metabolism*
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Sodium-Hydrogen Exchanger 1
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Sodium-Hydrogen Exchangers / genetics
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Sodium-Hydrogen Exchangers / metabolism*
Substances
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Cation Transport Proteins
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Muscle Proteins
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NAV1.5 Voltage-Gated Sodium Channel
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Protons
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SCN5A protein, human
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SLC9A1 protein, human
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Sodium Channels
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Sodium-Hydrogen Exchanger 1
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Sodium-Hydrogen Exchangers