ArticleThe Journal of clinical endocrinology and metabolism2013
Manipulation of PBF/PTTG1IP phosphorylation status; a potential new therapeutic strategy for improving radioiodine uptake in thyroid and other tumors.
Article in The Journal of clinical endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Microenvironmental Control of Thyroid Cancer Plasticity and Radioiodine Resistance.International journal of molecular sciences · 2026Review
- Targeting Src tyrosine kinase to enhance radioiodide uptake in breast cancer.Endocrine-related cancer · 2025Article
- Combined Vorinostat and Chloroquine Inhibit Sodium-Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Advances in the molecular mechanism and targeted therapy of radioactive-iodine refractory differentiated thyroid cancer.Medical oncology (Northwood, London, England) · 2023Review
- The effect of sodium iodide symporter protein on ablation success in patients with differentiated thyroid cancer.Annals of nuclear medicine · 2022Article
- Molecular mechanisms of resistance to kinase inhibitors and redifferentiation in thyroid cancers.Endocrine-related cancer · 2022Review
- Redox Homeostasis in Thyroid Cancer: Implications in NaInternational journal of molecular sciences · 2022Review
- Recurrence of Papillary Thyroid Cancer: A Systematic Appraisal of Risk Factors.The Journal of clinical endocrinology and metabolism · 2022Article
- Article
- Targeting non-canonical pathways as a strategy to modulate the sodium iodide symporter.Cell chemical biology · 2022Article
- Mechanisms of regulating NIS transport to the cell membrane and redifferentiation therapy in thyroid cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- Article
- Na+/I- symporter expression, function, and regulation in non-thyroidal tissues and impact on thyroid cancer therapy.Endocrine-related cancer · 2021Article
- Review
- Targeting Novel Sodium Iodide Symporter Interactors ADP-Ribosylation Factor 4 and Valosin-Containing Protein Enhances Radioiodine Uptake.Cancer research · 2020Article
- Dimerization of the Sodium/Iodide Symporter.Thyroid : official journal of the American Thyroid Association · 2019Article
- Implications of NaJournal of the Endocrine Society · 2019Review
- A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter.Endocrinology · 2019Article
- PTTG and PBF Functionally Interact with p53 and Predict Overall Survival in Head and Neck Cancer.Cancer research · 2018Article
- Article
Corrections and comments
- Commented on by
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
contextThe clinical effectiveness of ablative radioiodine treatment of thyroid tumors is limited by the availability of the sodium iodide symporter (NIS) at the plasma membrane (PM) for uptake of ¹³¹I. A significant proportion of well-differentiated thyroid tumors are unable to concentrate sufficient radioiodine for effective therapy, and in other tumor models such as breast tumors, where radioiodine uptake would be an attractive therapeutic option, uptake is insufficient.
objectivePituitary tumor-transforming gene-binding factor (PBF; PTTG1IP) is overexpressed in multiple cancers and significantly decreases NIS expression at the PM. The goal of this study was to identify a method by which PBF repression of NIS may be overcome in human tumors.
resultsHere, we identify PBF as a tyrosine phosphoprotein that specifically binds the proto-oncogene tyrosine protein kinase Src in mass spectrometry, glutathione S-transferase pulldown and coimmunoprecipitation assays. Src induction leads to phosphorylation at PBF residue Y174. Abrogation of this residue results in PM retention and a markedly reduced ability to bind NIS. The Src inhibitor PP1 inhibits PBF phosphorylation in multiple cell lines in vitro, including human primary thyroid cells. Of direct clinical importance to the treatment of thyroid cancer, PP1 stimulates iodide uptake by transfected NIS in TPC1 thyroid carcinoma cells and entirely overcomes PBF repression of iodide uptake in human primary thyroid cells.
conclusionsWe propose that targeting PBF phosphorylation at residue Y174 via tyrosine kinase inhibitors may be a novel therapeutic strategy to enhance the efficacy of ablative radioiodine treatment in thyroid and other endocrine and endocrine-related tumors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.