A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer

Vicki Smith, Martin Read, Andrew Turnell, Rachel Watkins, John Watkinson, Gregory Lewy, Jim Fong, SR James, Margaret Eggo, Kristien Boelaert, Jayne Franklyn, Christopher McCabe

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64 Citations (Scopus)


Differentiated thyroid cancers and their metastases frequently exhibit reduced iodide uptake, impacting on the efficacy of radioiodine ablation therapy. PTTG binding factor (PBF) is a proto-oncogene implicated in the pathogenesis of thyroid cancer. We recently reported that PBF inhibits iodide uptake, and have now elucidated a mechanism by which PBF directly modulates sodium iodide symporter (NIS) activity in vitro. In subcellular localisation studies, PBF overexpression resulted in the redistribution of NIS from the plasma membrane into intracellular vesicles, where it colocalised with the tetraspanin CD63. Cell-surface biotinylation assays confirmed a reduction in plasma membrane NIS expression following PBF transfection compared with vector-only treatment. Coimmunoprecipitation and GST-pull-down experiments demonstrated a direct interaction between NIS and PBF, the functional consequence of which was assessed using iodide-uptake studies in rat thyroid FRTL-5 cells. PBF repressed iodide uptake, whereas three deletion mutants, which did not localise within intracellular vesicles, lost the ability to inhibit NIS activity. In summary, we present an entirely novel mechanism by which the protooncogene PBF binds NIS and alters its subcellular localisation, thereby regulating its ability to uptake iodide. Given that PBF is overexpressed in thyroid cancer, these findings have profound implications for thyroid cancer ablation using radioiodine.
Original languageEnglish
Pages (from-to)3393-3402
Number of pages10
JournalJournal of Cell Science
Issue number18
Publication statusPublished - 1 Sept 2009

Bibliographical note

Rachel Spruce published under Rachel Watkins


  • PBF
  • Iodide uptake
  • Thyroid cancer
  • NIS


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