title: Organellar (Na+, K+)/H+ exchanger NHE7 regulates cell adhesion, invasion             and anchorage-independent growth of breast cancer MDA-MB-231 cells.
abstract: Na+/H+ exchangers (NHEs) are a group of secondary active antiporters that             regulate cellular pH, cell volume and ion homeostasis. In humans, nine isoforms             (NHE1-NHE9) were identified and characterized as functional NHEs. While a growing             body of evidence indicates that NHE1 generates an acidic tumor environment and             thereby contributes to tumor invasion, little is known about the role of other             NHE isoforms in tumor progression. NHE7 is a unique member of the NHE gene family             that dynamically shuttles between the trans-Golgi network, endosomes and the plasma             membrane, and regulates the luminal pH of these organelles. Here we show that             NHE7-overexpression in breast cancer MDA-MB-231 cells enhances cell overlay, cell-cell             adhesion, invasion, anchorage-independent tumor growth and tumor formation in vivo.             In contrast, NHE1-overexpression enhances tumor invasion, but it has little effect             on cell adhesion or anchorage-independent tumor growth. Pathological examinations             of the tumor samples derived from NHE7-overexpressing cells showed a similar appearance             to aggressive tumors. Together, these results suggest that NHE7 enhances tumor             progression. This is the first report to show the involvement of an organellar             NHE in oncogenic processes.
authors.affiliation: Department of Biochemistry and Molecular Biology, University                     of British Columbia, Vancouver, BC, Canada.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Onishi
authors.forename: Paulo J C
authors.initials: PJ
authors.lastname: Lin
authors.forename: Yuka
authors.initials: Y
authors.lastname: Numata
authors.forename: Pamela
authors.initials: P
authors.lastname: Austin
authors.forename: Jane
authors.initials: J
authors.lastname: Cipollone
authors.forename: Michel
authors.initials: M
authors.lastname: Roberge
authors.forename: Calvin D
authors.initials: CD
authors.lastname: Roskelley
authors.forename: Masayuki
authors.initials: M
authors.lastname: Numata
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D027682:Cation Transport Proteins; C490998:SLC9A1 protein, human; C429538:SLC9A7 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers