American Association for Cancer Research
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Supplementary Video 1 from Iodide Transporter NIS Regulates Cancer Cell Motility and Invasiveness by Interacting with the Rho Guanine Nucleotide Exchange Factor LARG

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posted on 2023-03-30, 21:00 authored by Claire Lacoste, Julie Hervé, Myriam Bou Nader, Alexandre Dos Santos, Nicolas Moniaux, Yannick Valogne, Rodrick Montjean, Olivier Dorseuil, Didier Samuel, Doris Cassio, Carla Portulano, Nancy Carrasco, Christian Bréchot, Jamila Faivre

MOV file - 1MB, Time lapse video microscopy of HEK293 cells transfected with empty



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. Cancer Res; 72(21); 5505–15. ©2012 AACR.

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