title: NHE1 is upregulated in gastric cancer and regulates gastric cancer cell proliferation, migration and invasion.
abstract: Na+/H+ exchanger isoform 1 (NHE1) is known to play a key role in regulating intracellular pH and osmotic homeostasis and is involved in the development and progression of several types of cancer. However, the function and specific mechanism of NHE1 in gastric cancer (GC) are not clearly understood. In the present study, we report that NHE1 is overexpressed in tissues and cell lines from GC patients, and knockdown or inhibition of NHE1 suppressed GC cell proliferation via regulation of G1/S and G2/M cell cycle phase transitions, concomitant with a marked decrease in positive cell cycle regulators, including cyclin D1 and cyclin B1. Likewise, NHE1 was required for GC cell migration and invasion through the regulation of epithelial-mesenchymal transition (EMT) proteins, and NHE1 inhibition resulted in an acidic intracellular environment, providing possible mechanisms underlying NHE1-mediated GC progression both in vitro and in vivo. These data highlight the important role of NHE1 in GC progression and suggest that NHE1 may be a useful target for GC therapy.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
authors.forename: Guorong
authors.initials: G
authors.lastname: Wen
authors.affiliation: Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
authors.forename: Biguang
authors.initials: B
authors.lastname: Tuo
authors.affiliation: Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D027682:Cation Transport Proteins; D012333:RNA, Messenger; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D019938:Cyclin D1