Affinage

SLC5A5

Sodium/iodide cotransporter · UniProt Q92911

Length
643 aa
Mass
68.7 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC5A5 (NIS) is the plasma membrane glycoprotein that mediates active iodide accumulation in thyroid follicular cells, originally defined by expression cloning of iodide transport activity in Xenopus oocytes (PMID:12588808, PMID:24311738, PMID:9672241). It catalyzes electrogenic Na+/I- symport with a stoichiometry of 2 Na+ per I-, energized by the electrochemical Na+ gradient that the Na+/K+-ATPase maintains; collapsing this gradient abolishes transport (PMID:9672241, PMID:12588808, PMID:24311738, PMID:19196800). NIS is a polyspecific transporter that can also translocate perchlorate, but does so with a distinct electroneutral Na+/ClO4- stoichiometry, demonstrating substrate-dependent coupling (PMID:18077370). Vectorial blood-to-lumen iodide transport requires selective basolateral targeting (PMID:12588808), which depends on N-glycosylation and cAMP-stimulated maturation (PMID:26599396), an internal PDZ-binding motif at position 121 whose mutation abolishes surface expression (PMID:26831514), and a C-terminal W-acidic motif recognized by kinesin light chain 2 (KLC2) that licenses ER exit; the G561E variant disrupts KLC2 recognition and blocks NIS maturation, with KLC2 loss reducing iodide accumulation in thyroid cells and thyroid hormone synthesis in zebrafish (PMID:33912899). Congenital iodide transport defect arises from point mutations such as Q267E and T354P that lower catalytic turnover without preventing membrane targeting (PMID:14734652, PMID:10403177). NIS transcription is controlled by a network of regulators acting through defined promoter and intronic elements: Pax8 (PMID:16029487), p53-family members at p53-responsive elements (PMID:24052075), retinoic acid receptor/RXR heterodimers at intronic RAREs (PMID:20123735), and CRE-dependent cAMP/AMPK input (PMID:23819433), while it is silenced in cancer by BRAF V600E-driven histone deacetylation (PMID:24243688), distal enhancer DNA methylation (PMID:24432988), and miR-146b-3p-mediated 3'-UTR translational repression (PMID:26282166). Beyond ion transport, NIS physically binds the Rho-GEF LARG to activate RhoA signaling and promote cancer cell migration and invasion, a transport-independent function enhanced when NIS is sequestered intracellularly (PMID:22962269).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1996 High

    Established the molecular identity of the long-sought thyroid iodide transporter, converting a physiological activity into a defined gene product.

    Evidence Expression cloning in Xenopus oocytes with functional iodide uptake

    PMID:12588808 PMID:24311738 PMID:9672241

    Open questions at the time
    • Did not resolve transport stoichiometry or driving force
    • No structural model of the transporter
  2. 1998 High

    Defined the energetic mechanism of iodide accumulation by quantifying the ion coupling, explaining how NIS concentrates iodide against its gradient.

    Evidence Electrophysiological analysis (two-electrode voltage clamp)

    PMID:12588808 PMID:24311738 PMID:9672241

    Open questions at the time
    • Did not address whether other substrates share the same stoichiometry
    • No residue-level mechanism of ion coupling
  3. 2003 High

    Showed that NIS function is coupled to the Na+/K+-ATPase-maintained gradient and that the protein is selectively basolateral, linking energetics to vectorial transport physiology.

    Evidence Na+/K+-ATPase inhibition with uptake assays; immunolocalization and membrane fractionation

    PMID:12588808 PMID:19196800

    Open questions at the time
    • Did not identify the trafficking determinants of basolateral sorting
  4. 2004 High

    Distinguished catalytic from trafficking defects in disease mutants, showing that ITD mutations such as Q267E reduce turnover rather than block membrane targeting.

    Evidence Site-directed mutagenesis and iodide uptake in COS-7 cells with immunofluorescence

    PMID:14734652

    Open questions at the time
    • Mechanism by which position 267 controls turnover unresolved
    • No structural basis for charge intolerance
  5. 2007 High

    Demonstrated that NIS is polyspecific and that coupling stoichiometry is substrate-dependent, reframing perchlorate as a transported substrate rather than a pure inhibitor.

    Evidence In vitro/in vivo uptake assays with mathematical flux modeling

    PMID:18077370

    Open questions at the time
    • Structural basis for differential stoichiometry unknown
  6. 2016 High

    Systematically mapped trafficking motifs, identifying the position-121 PDZ-binding motif as essential for surface expression and position 178 for transport.

    Evidence Mutagenesis of sorting motifs with surface expression and iodide uptake readouts

    PMID:26831514

    Open questions at the time
    • Identity of the PDZ partner not established
    • C-terminal motif function clarified only later
  7. 2021 High

    Identified KLC2 as a trafficking partner recognizing a C-terminal W-acidic motif required for NIS ER exit, providing a molecular route for a disease variant.

    Evidence Co-IP, mutagenesis, KLC2 siRNA in rat thyroid cells, and zebrafish morpholino knockdown

    PMID:33912899

    Open questions at the time
    • Reconciliation with earlier finding that C-terminal motifs were dispensable for targeting
    • No structure of the NIS-KLC2 interface
  8. 2012 Medium

    Revealed a transport-independent role for NIS in promoting cancer cell motility through LARG/RhoA signaling, expanding NIS function beyond ion transport.

    Evidence Co-IP of NIS-LARG plus migration/invasion assays in cancer cell lines

    PMID:22962269

    Open questions at the time
    • Single Co-IP without reciprocal validation in multiple systems
    • Structural basis of NIS-LARG binding unknown
    • In vivo metastasis relevance not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NIS trafficking, transport catalysis, and its non-canonical LARG/RhoA signaling are integrated at the structural level, and how cytosolic NIS in extrathyroidal tissues functions, remain open.
  • No experimental structure
  • Function of cytosolic NIS in testis undefined
  • Determinants selecting transport vs signaling roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140104 molecular carrier activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-382551 Transport of small molecules 4
Partners
KLC2LARGPAX8

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 NIS (SLC5A5) was isolated by expression cloning in Xenopus laevis oocytes, establishing it as the plasma membrane protein mediating active iodide transport into thyroid follicular cells. Expression cloning in Xenopus oocytes Nature (referenced in corpus reviews) High 12588808 24311738 9672241
1998 NIS mediates electrogenic active transport with a stoichiometry of 2 Na+ ions co-transported per 1 iodide ion, as determined by electrophysiological analysis. Electrophysiological analysis (two-electrode voltage clamp and related assays) Journal of bioenergetics and biomembranes High 12588808 24311738 9672241
2007 NIS actively transports perchlorate (ClO4-) as a substrate (not merely a competitive inhibitor), but with an electroneutral Na+/ClO4- stoichiometry—different from the electrogenic 2 Na+/I- stoichiometry—demonstrating that NIS translocates different substrates with different stoichiometries. In vitro iodide/perchlorate uptake assays, in vivo translocation to milk, mathematical flux modeling Proceedings of the National Academy of Sciences of the United States of America High 18077370
2004 The Q267E NIS mutation causes congenital iodide transport defect (ITD) by reducing the catalytic turnover number (lower Vmax) rather than by preventing plasma membrane targeting; neutral substitutions at position 267 are compatible with partial activity, but any charged residue (of either polarity) other than Gln renders NIS inactive without affecting expression or membrane targeting. Site-directed mutagenesis, iodide uptake assays, COS-7 cell transfection, immunofluorescence Journal of cell science High 14734652
2003 NIS is selectively targeted to the basolateral membrane of thyroid follicular cells, enabling vectorial iodide transport from blood to the follicular lumen, as established by immunolocalization and functional fractionation studies. Immunohistochemistry, immunofluorescence, membrane fractionation Endocrine reviews High 12588808
2003 NIS-mediated iodide transport is driven by the electrochemical sodium gradient generated by the Na+/K+-ATPase; disruption of this gradient abolishes NIS function. Pharmacological inhibition of Na+/K+-ATPase combined with iodide uptake assays Endocrine reviews High 12588808 19196800
2015 Glycosylation of NIS regulates its membrane translocation and radioiodine uptake: cAMP-stimulated glycosylation promotes NIS plasma membrane targeting and enhances iodide uptake, while inhibition of glycosylation with tunicamycin dramatically reduces NIS membrane localization and uptake. Confocal microscopy of NIS/tdTomato fusion protein, radioiodine uptake assay, immunoblot, tunicamycin inhibition, cAMP stimulation in stably transfected HeLa cells PloS one Medium 26599396
2021 A G561E missense variant in NIS impairs recognition of an adjacent tryptophan-acidic (W-acidic) motif by kinesin light chain 2 (KLC2), blocking NIS maturation beyond the endoplasmic reticulum and reducing plasma membrane targeting and iodide accumulation; KLC2 knockdown phenocopies this defect in rat thyroid cells and reduces thyroid hormone synthesis in zebrafish larvae. Site-directed mutagenesis, iodide uptake assay, co-immunoprecipitation (NIS–KLC2 interaction), KLC2 siRNA knockdown in rat thyroid cells, morpholino knockdown in zebrafish, structural bioinformatics The Journal of clinical endocrinology and metabolism High 33912899
2012 NIS (SLC5A5) interacts physically with the Rho guanine nucleotide exchange factor LARG (leukemia-associated RhoA GEF), thereby activating RhoA signaling to enhance cancer cell migration and invasion independently of its ion transport activity; sequestration of NIS in intracellular organelles (as observed in many cancers) further increases cell motility and invasiveness. Co-immunoprecipitation (NIS–LARG interaction), cell migration and invasion assays, intracellular NIS targeting constructs in cancer cell lines Cancer research Medium 22962269
2016 Systematic mutagenesis of trafficking motifs in human NIS identified that mutation of an internal PDZ-binding motif at position 121 completely abolishes NIS expression at the plasma membrane; mutation at position 178 (SH2/tyrosine-based motif) impairs iodide uptake; C-terminal domain motifs are dispensable for membrane targeting. Site-directed mutagenesis of sorting motifs combined with iodide uptake assays and cell surface expression analysis The Biochemical journal High 26831514
2010 Retinoic acid (tRA) directly induces NIS transcription through retinoic acid receptor alpha (RARα)/retinoid-X-receptor (RXR) heterodimers binding to conserved retinoic acid response elements (RAREs) located within the first intron of the NIS gene, as demonstrated by ChIP and in vitro/in vivo DNA-protein interaction assays in MCF-7 breast cancer cells. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), reporter gene assays, luciferase transcription assays Nucleic acids research High 20123735
2013 NIS is a direct transcriptional target of p53-family members (p53, p63, p73): these factors bind p53-responsive element clusters in the NIS core promoter (shown by ChIP), stimulate NIS promoter activity and endogenous NIS mRNA/protein expression, and doxorubicin-induced DNA damage strongly increases p53/p73 binding to the NIS promoter in HCC and CCA cells. NIS silencing reduces doxorubicin-induced apoptosis in HCC cells. Chromatin immunoprecipitation (ChIP), siRNA knockdown, reporter gene assay, Western blot, RT-PCR in liver cancer cell lines Cell death & disease High 24052075
2014 BRAF V600E promotes NIS silencing via histone deacetylation at critical regulatory regions (nucleotides -297/-107 in rat, -692/-370 in human NIS promoter); pharmacological inhibition of BRAF V600E or MEK restores histone acetylation at the NIS promoter, and HDAC inhibitor SAHA reverses deacetylation and restores NIS expression. Chromatin immunoprecipitation (ChIP) for H3K9/14ac, H3K18ac, H4ac, H4K16ac; stable BRAF V600E transfection in PCCL3 cells; BRAF and MEK inhibitors in BCPAP cells Endocrine-related cancer High 24243688
2013 AMPK modulates NIS expression and iodide uptake in thyroid cells via the CRE (cAMP response element) in the NIS promoter: AMPK activation (metformin) reduces NIS promoter activity via CRE and decreases iodide uptake, while AMPK inhibition (compound C) stimulates CRE-mediated NIS transcription and iodide uptake both in vitro and in vivo. NIS promoter-reporter constructs with isolated CRE and NF-κB elements, iodide uptake assays, NIS Western blot, in vivo mouse studies, AMPK-α1 knockout mice Thyroid Medium 23819433
2015 miR-146b-3p directly binds the 3'-UTR of both PAX8 and NIS mRNAs, inhibiting their translation and reducing iodide uptake; miR-146b and PAX8 mutually regulate each other, forming a regulatory circuit governing thyroid cell differentiation in papillary thyroid carcinoma. 3'-UTR luciferase reporter assay (direct miR-146b-3p binding to PAX8 and NIS 3'-UTR), next-generation sequencing, mRNA sequencing, iodide uptake assay in thyroid cancer cell lines Cancer research High 26282166
2006 In MCF-7 breast cancer cells, hydrocortisone and ATP (via purinergic signaling) each markedly stimulate retinoic acid-induced NIS protein expression and plasma membrane targeting, increasing iodide uptake by at least 100%; conversely, forskolin (adenylyl cyclase activator) decreases retinoic acid-induced NIS expression in MCF-7 cells—opposite to its effect in thyroid cells—indicating tissue-specific cAMP regulation of NIS. Iodide uptake assay, Western blot, pharmacological stimulation in MCF-7 cells Molecular endocrinology Medium 16439463
2014 A newly identified distal NIS enhancer (NDE), located at -2152/-1887 relative to ATG, regulates NIS expression via DNA methylation; hypermethylation of this enhancer in thyroid tumors correlates inversely with NIS mRNA expression, and demethylation with 5-Aza restores NIS mRNA, protein, and iodide uptake. Bisulfite sequencing, reporter gene assay (confirming enhancer activity), 5-Aza demethylation treatment with RT-PCR, Western blot, and 125I uptake assay in matched tumor/non-tumor samples The Journal of clinical endocrinology and metabolism High 24432988
2009 NIS is expressed at the basolateral membrane of gastric mucin-producing epithelial cells; NIS expression is absent in gastric cancer and in Barrett mucosa with intestinal metaplasia, but present in Barrett mucosa with fundic/junctional columnar metaplasia, establishing NIS localization and its loss during intestinalization or malignant transformation of gastric mucosa. Immunohistochemistry and immunoblot in 155 gastrointestinal tissue samples from 83 patients BMC cancer Medium 17214887
2005 Overexpression of transcription factor Pax8 in anaplastic thyroid carcinoma ARO cells reactivates NIS expression and partial membrane targeting (confirmed by immunofluorescence and Western blot), restoring partial radioiodide uptake ability, demonstrating Pax8 as a transcriptional regulator required for NIS expression. Stable transfection with Pax8 expression vector, quantitative RT-PCR, Western blot, immunofluorescence, iodide uptake assay BMC cancer Medium 16029487
2009 Radiation-induced stunning of thyroid cells reduces iodide transport and NIS mRNA expression; all tested NIS-transported radionuclides (123I, 131I, 99mTc, 211At) caused downregulation, with the degree of NIS mRNA reduction related to the biological effectiveness of the radiation type. 211At caused the highest per-dose stunning but also the only full recovery of transport. Quantitative RT-PCR for NIS mRNA, iodide transport assay in TSH-stimulated thyroid cell monolayers exposed to defined absorbed doses of radionuclides Journal of nuclear medicine Medium 19525464
2011 NIS protein is expressed in germinal and Leydig cells of normal testis (but not Sertoli cells), predominantly in the cytosol compartment rather than at the plasma membrane, as determined by Western blot and immunohistochemistry in mouse, rat, and human testicular tissue. Quantitative RT-PCR, Western blot, immunohistochemistry in fetal and adult testicular tissue from three species Endocrine Medium 21499816
1999 Six NIS mutations causing congenital iodide transport defect (G93R, Q267E, C272X, T354P, Y531X, G543E) produce NIS proteins with no or minimal iodide transport activity when expressed in mammalian cells; critically, T354P does not prevent membrane targeting but specifically impairs transport function, while co-transfection of mutant with wild-type NIS shows no dominant-negative interference. Mammalian cell transfection, iodide uptake assay, co-transfection with wild-type NIS Biochimie Medium 10403177

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocrine reviews 611 12588808
2013 The Na+/I- symporter (NIS): mechanism and medical impact. Endocrine reviews 215 24311738
2017 The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications. Annual review of physiology 202 28192058
2009 Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Endocrinology 146 19196800
2012 The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics. Pharmacology & therapeutics 144 22750642
2007 The Na+/I symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate. Proceedings of the National Academy of Sciences of the United States of America 140 18077370
2003 Advances in Na(+)/I(-) symporter (NIS) research in the thyroid and beyond. Molecular and cellular endocrinology 130 15062574
2021 Molecular mechanisms of radioactive iodine refractoriness in differentiated thyroid cancer: Impaired sodium iodide symporter (NIS) expression owing to altered signaling pathway activity and intracellular localization of NIS. Theranostics 125 33995657
2002 Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation? BMC cancer 109 12475396
2012 The sodium iodide symporter (NIS) as an imaging reporter for gene, viral, and cell-based therapies. Current gene therapy 106 22263922
2015 The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis. Cancer research 87 26282166
2004 The Na/I symporter (NIS): imaging and therapeutic applications. Seminars in nuclear medicine 81 14735456
2014 Histone deacetylation of NIS promoter underlies BRAF V600E-promoted NIS silencing in thyroid cancer. Endocrine-related cancer 77 24243688
2019 Development of measures of polyneuropathy impairment in hATTR amyloidosis: From NIS to mNIS + 7. Journal of the neurological sciences 75 31445300
2011 Image-guided, tumor stroma-targeted 131I therapy of hepatocellular cancer after systemic mesenchymal stem cell-mediated NIS gene delivery. Molecular therapy : the journal of the American Society of Gene Therapy 75 21587211
2010 Sodium iodide symporter (NIS)-mediated radiovirotherapy for pancreatic cancer. AJR. American journal of roentgenology 67 20651188
2008 Epigenetic silencing of O6-methylguanine DNA methyltransferase gene in NiS-transformed cells. Carcinogenesis 67 18204074
2017 Iodide handling disorders (NIS, TPO, TG, IYD). Best practice & research. Clinical endocrinology & metabolism 62 28648508
2014 Retrospective study of a TTR FAP cohort to modify NIS+7 for therapeutic trials. Journal of the neurological sciences 60 25012480
1998 The Na+/I- symporter (NIS): recent advances. Journal of bioenergetics and biomembranes 60 9672241
2015 The use of the NIS reporter gene for optimizing oncolytic virotherapy. Expert opinion on biological therapy 56 26457362
2001 Journey of the iodide transporter NIS: from its molecular identification to its clinical role in cancer. Trends in biochemical sciences 56 11504625
2022 Perchlorate, nitrate, and thiocyanate: Environmental relevant NIS-inhibitors pollutants and their impact on thyroid function and human health. Frontiers in endocrinology 54 36339434
2010 Genetics and phenomics of hypothyroidism and goiter due to NIS mutations. Molecular and cellular endocrinology 52 20153805
2015 BRAF V600E and decreased NIS and TPO expression are associated with aggressiveness of a subgroup of papillary thyroid microcarcinoma. European journal of endocrinology 51 26338373
2014 Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics. Journal of molecular endocrinology 49 24353283
2012 MicroRNA-152 targets DNA methyltransferase 1 in NiS-transformed cells via a feedback mechanism. Carcinogenesis 49 23125218
2004 The Q267E mutation in the sodium/iodide symporter (NIS) causes congenital iodide transport defect (ITD) by decreasing the NIS turnover number. Journal of cell science 49 14734652
1999 Mutations in the sodium/iodide symporter (NIS) gene as a cause for iodide transport defects and congenital hypothyroidism. Biochimie 49 10403177
2011 Sodium iodide symporter (NIS)-mediated radionuclide ((131)I, (188)Re) therapy of liver cancer after transcriptionally targeted intratumoral in vivo NIS gene delivery. Human gene therapy 44 21488714
2019 Fluoride Exposure Induces Inhibition of Sodium/Iodide Symporter (NIS) Contributing to Impaired Iodine Absorption and Iodine Deficiency: Molecular Mechanisms of Inhibition and Implications for Public Health. International journal of environmental research and public health 43 30917615
2007 Expression of the Na+/I- symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus. BMC cancer 43 17214887
2012 Iodide transporter NIS regulates cancer cell motility and invasiveness by interacting with the Rho guanine nucleotide exchange factor LARG. Cancer research 42 22962269
2014 Sodium iodide symporter (NIS) in extrathyroidal malignancies: focus on breast and urological cancer. BMC cancer 39 24884806
2014 Hypermethylation of a New Distal Sodium/Iodide Symporter (NIS) enhancer (NDE) is associated with reduced NIS expression in thyroid tumors. The Journal of clinical endocrinology and metabolism 38 24432988
2021 The complex regulation of NIS expression and activity in thyroid and extrathyroidal tissues. Endocrine-related cancer 37 34387194
2007 The importance of sodium/iodide symporter (NIS) for thyroid cancer management. Arquivos brasileiros de endocrinologia e metabologia 37 17891230
2003 Functional expression of sodium iodide symporter (NIS) in human breast cancer tissue. Breast cancer research and treatment 37 12602914
1998 Implications of the molecular characterization of the sodium-iodide symporter (NIS). Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 37 9865544
2006 Hydrocortisone and purinergic signaling stimulate sodium/iodide symporter (NIS)-mediated iodide transport in breast cancer cells. Molecular endocrinology (Baltimore, Md.) 36 16439463
2009 Radiation-induced thyroid stunning: differential effects of (123)I, (131)I, (99m)Tc, and (211)At on iodide transport and NIS mRNA expression in cultured thyroid cells. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 35 19525464
2016 MicroRNAs let7 expression in thyroid cancer: correlation with their deputed targets HMGA2 and SLC5A5. Journal of cancer research and clinical oncology 33 26960757
2013 Impact of Metformin and compound C on NIS expression and iodine uptake in vitro and in vivo: a role for CRE in AMPK modulation of thyroid function. Thyroid : official journal of the American Thyroid Association 33 23819433
2012 Sodium iodide symporter (NIS)-mediated radiovirotherapy of hepatocellular cancer using a conditionally replicating adenovirus. Gene therapy 33 23038026
2001 Sodium/iodide symporter (NIS) and pendrin are expressed differently in hot and cold nodules of thyroid toxic multinodular goiter. European journal of endocrinology 33 11720877
2021 The sodium iodide symporter (NIS): novel applications for radionuclide imaging and treatment. Endocrine-related cancer 32 34259647
2018 Epigenetic Modifications in Thyroid Cancer Cells Restore NIS and Radio-Iodine Uptake and Promote Cell Death. Journal of clinical medicine 31 29561759
2018 mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression. International journal of molecular sciences 31 29757257
2017 Imaging and targeted therapy of pancreatic ductal adenocarcinoma using the theranostic sodium iodide symporter (NIS) gene. Oncotarget 31 28380420
2015 Glycosylation of Sodium/Iodide Symporter (NIS) Regulates Its Membrane Translocation and Radioiodine Uptake. PloS one 31 26599396
2021 miR-221-3p and miR-222-3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer. Experimental and therapeutic medicine 29 33968182
2018 NiS1.03 Hollow Spheres and Cages as Superhigh Rate Capacity and Stable Anode Materials for Half/Full Sodium-Ion Batteries. ACS nano 29 30004665
2017 The rhizoferrin biosynthetic gene in the fungal pathogen Rhizopus delemar is a novel member of the NIS gene family. The international journal of biochemistry & cell biology 29 28610916
2012 Induction of sodium/iodide symporter (NIS) expression and radioiodine uptake in non-thyroid cancer cells. PloS one 29 22359623
2022 Effect of intrathecal NIS-lncRNA antisense oligonucleotides on neuropathic pain caused by nerve trauma, chemotherapy, or diabetes mellitus. British journal of anaesthesia 28 36460518
2018 A Novel Approach for Image-Guided 131I Therapy of Pancreatic Ductal Adenocarcinoma Using Mesenchymal Stem Cell-Mediated NIS Gene Delivery. Molecular cancer research : MCR 27 30224540
2016 Sequence-defined cMET/HGFR-targeted Polymers as Gene Delivery Vehicles for the Theranostic Sodium Iodide Symporter (NIS) Gene. Molecular therapy : the journal of the American Society of Gene Therapy 27 27157666
2011 The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue. PloS one 27 21283523
2005 Recovery of NIS expression in thyroid cancer cells by overexpression of Pax8 gene. BMC cancer 26 16029487
2023 Flower-Like NiS2 /WS2 Heterojunction as Polysulfide/sulfide Bidirectional Catalytic Layer for High-Performance Lithium-Sulfur Batteries. Small (Weinheim an der Bergstrasse, Germany) 25 36658717
2018 The Role of the NIS (SLC5A5) Gene in Papillary Thyroid Cancer: A Systematic Review. International journal of endocrinology 25 30595693
2011 Expression and localization of the sodium/iodide symporter (NIS) in testicular cells. Endocrine 24 21499816
2009 Endogenous NIS expression in triple-negative breast cancers. Annals of surgical oncology 24 19184238
2019 A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity. International journal of nanomedicine 23 30880979
2022 Redox Homeostasis in Thyroid Cancer: Implications in Na+/I- Symporter (NIS) Regulation. International journal of molecular sciences 22 35682803
2021 The flavonoid quercetin reduces cell migration and increases NIS and E-cadherin mRNA in the human thyroid cancer cell line BCPAP. Molecular and cellular endocrinology 22 33831503
2019 Dual-targeted NIS polyplexes-a theranostic strategy toward tumors with heterogeneous receptor expression. Gene therapy 22 30683895
2019 TGFB1-driven mesenchymal stem cell-mediated NIS gene transfer. Endocrine-related cancer 21 30121623
2001 Sodium/iodide symporter (NIS) and cytokines. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 20 11573136
2019 Radiation-Induced Amplification of TGFB1-Induced Mesenchymal Stem Cell-Mediated Sodium Iodide Symporter (NIS) Gene 131I Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 19 31196853
2018 Reverting iodine avidity of radioactive-iodine refractory thyroid cancer with a new tyrosine kinase inhibitor (K905-0266) excavated by high-throughput NIS (sodium iodide symporter) enhancer screening platform using dual reporter gene system. Oncotarget 19 29467951
2018 Synergistic inhibition of MEK/ERK and BRAF V600E with PD98059 and PLX4032 induces sodium/iodide symporter (NIS) expression and radioiodine uptake in BRAF mutated papillary thyroid cancer cells. Thyroid research 19 30337961
2013 The sodium/iodide symporter NIS is a transcriptional target of the p53-family members in liver cancer cells. Cell death & disease 19 24052075
2012 Methylation levels of sodium-iodide symporter (NIS) promoter in benign and malignant thyroid tumors with reduced NIS expression. Endocrine 19 22945693
1990 Uptake and biological transformation of beta NiS and alpha Ni3S2 by human embryonic pulmonary epithelial cells (L132) in culture. Carcinogenesis 19 2225326
2022 The sodium iodide symporter (NIS) as theranostic gene: its emerging role in new imaging modalities and non-viral gene therapy. EJNMMI research 18 35503582
2021 A Novel SLC5A5 Variant Reveals the Crucial Role of Kinesin Light Chain 2 in Thyroid Hormonogenesis. The Journal of clinical endocrinology and metabolism 18 33912899
2018 Effect of Combined Epigenetic Treatments and Ectopic NIS Expression on Undifferentiated Thyroid Cancer Cells. Anticancer research 18 30504373
2012 The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic marks in thyroid cancer cell lines. Molecular and cellular endocrinology 18 22982218
2010 Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription. Nucleic acids research 18 20123735
2020 Status and prospects of marine NIS detection and monitoring through (e)DNA metabarcoding. The Science of the total environment 17 32889465
2020 Hyaluronan oligosaccharides modulate inflammatory response, NIS and thyreoglobulin expression in human thyrocytes. Archives of biochemistry and biophysics 17 32976824
2011 Telomerase-driven expression of the sodium iodide symporter (NIS) for in vivo radioiodide treatment of cancer: a new broad-spectrum NIS-mediated antitumor approach. The Journal of clinical endocrinology and metabolism 17 21697253
2024 Mo-doping and construction of the heterostructure between NiFe LDH and NiSx co-trigger the activity enhancement for overall water splitting. Journal of colloid and interface science 16 38508033
2023 Improved Alkaline Seawater Splitting of NiS Nanosheets by Iron Doping. Inorganic chemistry 16 37144756
2023 Transcriptome profiling reveals SLC5A5 regulates chicken ovarian follicle granulosa cell proliferation, apoptosis, and steroid hormone synthesis. Poultry science 16 37980745
2021 Selective sodium iodide symporter (NIS) genetherapy of glioblastoma mediatedby EGFR-targeted lipopolyplexes. Molecular therapy oncolytics 16 34853814
2020 First case of fetal goitrous hypothyroidism due to SLC5A5/NIS mutations. European journal of endocrinology 16 32805706
2016 A systematic evaluation of sorting motifs in the sodium-iodide symporter (NIS). The Biochemical journal 16 26831514
2023 Mesenchymal Stem Cell-mediated Image-guided Sodium Iodide Symporter (NIS) Gene Therapy Improves Survival of Glioblastoma-bearing Mice. Clinical cancer research : an official journal of the American Association for Cancer Research 15 36516189
2019 Enhanced noninvasive imaging of oncology models using the NIS reporter gene and bioluminescence imaging. Cancer gene therapy 15 30674994
2019 Dual-Isotope SPECT Imaging with NIS Reporter Gene and Duramycin to Visualize Tumor Susceptibility to Oncolytic Virus Infection. Molecular therapy oncolytics 15 31890867
2018 LARP7 in papillary thyroid carcinoma induces NIS expression through suppression of the SHH signaling pathway. Molecular medicine reports 15 29620212
2004 Genetically targeted radiotherapy of head and neck squamous cell carcinoma using the sodium-iodide symporter (NIS). Head & neck 15 14999802
2022 Robust visible light active CoNiO2-BiFeO3-NiS ternary nanocomposite for photo-fenton degradation of rhodamine B and methyl orange: Kinetics, degradation pathway and toxicity assessment. Journal of environmental management 14 35751232
2018 A Novel Missense Mutation in the SLC5A5 Gene in a Sudanese Family with Congenital Hypothyroidism. Thyroid : official journal of the American Thyroid Association 14 29759035
2017 EGFR-targeted nonviral NIS gene transfer for bioimaging and therapy of disseminated colon cancer metastases. Oncotarget 14 29190908
2010 Stimulation of retinoic acid-induced functional sodium iodide symporter (NIS) expression and cytotoxicity of ¹³¹I by carbamazepine in breast cancer cells. Breast cancer research and treatment 14 20300827
2024 NIS-Seq enables cell-type-agnostic optical perturbation screening. Nature biotechnology 13 39702735
2010 Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model. Cancer gene therapy 13 20186172

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