Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation-independent manner
| Autor: | Pérez Torras, Sandra, Vidal Pla, Anna, Cano Soldado, Pedro Javier, Huber Ruano, Isabel, Mazo Sánchez, Adela, Pastor Anglada, Marçal |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2013 |
| Předmět: |
hCNT1
Cell death Cell Survival MAP Kinase Signaling System Genetic Vectors Gene Expression Adenocarcinoma Cell cycle Cicle cel·lular Adenoviridae transceptor Cell Line Tumor cell signaling Humans Extracellular Signal-Regulated MAP Kinases Càncer Cell Shape Cancer nucleoside transporter Cell Death Nucleotides Cell Cycle Membrane Transport Proteins Biological Transport Nucleosides Transport biològic Tumor Burden Pancreatic Neoplasms Nucleòtids Phenotype Mort cel·lular Original Article Biological transport Proto-Oncogene Proteins c-akt Neoplasm Transplantation |
| Zdroj: | CELL DEATH & DISEASE r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname Recercat. Dipósit de la Recerca de Catalunya Dipòsit Digital de la UB Universidad de Barcelona Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs play specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP ribose) polymerase hyperactivation and cell death, and reduced tumor growth and cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. These data predict a novel and totally unexpected biological role for the nucleoside transporter protein hCNT1 that appears to be independent of its role as mediator of nucleoside uptake by cells, thereby suggesting a transceptor function. Cell Death & Disease Anastasis Stephanou Receiving Editor Cell Death & Disease 19th Apr 2013 Dr Perez-Torras Av/ Diagonal 643. Edif. Prevosti, Pl -1 Barcelona 08028 Spain RE: Manuscript CDDIS-13-0136R, 'CDDIS-13-0136R' Dear Dr Perez-Torras, It is a pleasure to inform you that your manuscript has been evaluated at the editorial level and has now been officially accepted for publication in Cell Death & Disease, pending you meet the following editorial requirements: 1) the list of the abbreviations is missing please include Could you send us the revised text as word file via e-mail and we will proceed and transfer the paper onto our typesetters. Please download, print, sign, and return the Licence to Publish Form using the link below. This must be returned via FAX to ++ 39 06 7259 6977 before your manuscript can be published |
| Databáze: | OpenAIRE |
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