title: Iodide transporter NIS regulates cancer cell motility and invasiveness by interacting with the Rho guanine nucleotide exchange factor LARG.
abstract: A number of solute carrier (SLC) proteins are subject to changes in expression and activity during carcinogenesis. Whether these changes play a role in carcinogenesis is unclear, except for some nutrients and ion carriers whose deregulation ensures the necessary reprogramming of energy metabolism in cancer cells. In this study, we investigated the functional role in tumor progression of the sodium/iodide symporter (NIS; aka SLC5A5), which is upregulated and mislocalized in many human carcinomas. Notably, we found that NIS enhanced cell migration and invasion without ion transport being involved. These functions were mediated by NIS binding to leukemia-associated RhoA guanine exchange factor, a Rho guanine exchange factor that activates the small GTPase RhoA. Sequestering NIS in intracellular organelles or impairing its targeting to the cell surface (as observed in many cancers) led to a further increase in cell motility and invasiveness. In sum, our results established NIS as a carrier protein that interacts with a major cell signaling hub to facilitate tumor cell locomotion and invasion.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U785, Centre Hépatobiliaire, Hôpital Paul Brousse, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lacoste
authors.forename: Julie
authors.initials: J
authors.lastname: Hervé
authors.forename: Myriam
authors.initials: M
authors.lastname: Bou Nader
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dos Santos
authors.forename: Nicolas
authors.initials: N
authors.lastname: Moniaux
authors.forename: Yannick
authors.initials: Y
authors.lastname: Valogne
authors.forename: Rodrick
authors.initials: R
authors.lastname: Montjean
authors.forename: Olivier
authors.initials: O
authors.lastname: Dorseuil
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Doris
authors.initials: D
authors.lastname: Cassio
authors.forename: Carla
authors.initials: C
authors.lastname: Portulano
authors.forename: Nancy
authors.initials: N
authors.lastname: Carrasco
authors.forename: Christian
authors.initials: C
authors.lastname: Bréchot
authors.forename: Jamila
authors.initials: J
authors.lastname: Faivre
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005455:Fluorescent Antibody Technique; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D009361:Neoplasm Invasiveness / Q000473:pathology*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000502:physiology*; D027981:Symporters / Q000378:metabolism*; D014161:Transduction, Genetic; D020798:Two-Hybrid System Techniques; D000099209:Sodium-Iodide Symporters
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C577222:ARHGEF12 protein, human