Institut National de la Santé et de la Recherche Médicale (INSERM) U785, Centre Hépatobiliaire, Hôpital Paul Brousse, France.
Cancer Res. 2012 Nov 1;72(21):5505-15. doi: 10.1158/0008-5472.CAN-12-0516. Epub 2012 Sep 7.
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.
许多溶质载体（SLC）蛋白在癌变过程中表达和活性发生变化。除了一些营养物质和离子载体，它们的失调确保了癌细胞中能量代谢的必要重编程，这些变化在癌变中的作用尚不清楚。在这项研究中，我们研究了钠/碘同向转运体（NIS；又名 SLC5A5）在肿瘤进展中的功能作用，该蛋白在许多人类癌中上调和定位错误。值得注意的是，我们发现 NIS 增强了细胞迁移和侵袭，而不涉及离子转运。这些功能是通过 NIS 与白血病相关的 RhoA 鸟嘌呤核苷酸交换因子结合介导的，该 RhoA 鸟嘌呤核苷酸交换因子激活小 GTP 酶 RhoA。将 NIS 隔离在细胞内细胞器中或破坏其靶向细胞膜（如许多癌症中观察到的）会导致细胞迁移和侵袭性进一步增加。总之，我们的结果确立了 NIS 作为一种载体蛋白，它与主要的细胞信号枢纽相互作用，促进肿瘤细胞的运动和侵袭。
