title: The Na+/H+ exchanger NHE1, but not the Na+, HCO3(-) cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2.
abstract: We and others have shown central roles of the Na(+)/H(+) exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (ΔNErbB2). ΔNErbB2 expression elicited NBCn1 upregulation, Ser(703)-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of β1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ΔNErbB2. Adhesion and migration on collagen-I were augmented by ΔNErbB2, unaffected by the NBC inhibitor S0859, and further stimulated by EIPA in a manner potentiated by PI3K-Akt-inhibition. These findings demonstrate that NHE1 inhibition can enhance cancer cell motility, adding an important facet to the understanding of NHE1 in cancer.
authors: Section for Cell and Developmental Biology, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors: Gitte
authors: G
authors: Lauritzen
authors: Christian-Martin
authors: CM
authors: Stock
authors: Justine
authors: J
authors: Lemaire
authors: Stine F
authors: SF
authors: Lund
authors: Mie Frid
authors: MF
authors: Jensen
authors: Britt
authors: B
authors: Damsgaard
authors: Katrine Seide
authors: KS
authors: Petersen
authors: Maria
authors: M
authors: Wiwel
authors: Lone
authors: L
authors: Rønnov-Jessen
authors: Albrecht
authors: A
authors: Schwab
authors: Stine Falsig
authors: SF
authors: Pedersen
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D019012:Integrin beta1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D027982:Sodium-Bicarbonate Symporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D000099149:Ezrin
chemical_list: D000584:Amiloride; D001549:Benzamides; D027682:Cation Transport Proteins; D002867:Chromones; D016895:Culture Media, Serum-Free; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D019012:Integrin beta1; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D027982:Sodium-Bicarbonate Symporters; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013449:Sulfonamides; D000099149:Ezrin; C528718:S 0859 compound; C422022:SLC4A7 protein, human; C490998:SLC9A1 protein, human; C071058:moesin; C071776:radixin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C039614:ethylisopropylamiloride