Evidence map›Paper›PMID 24712572›Full record

ArticleThe Journal of clinical endocrinology and metabolism2014

mTOR Inhibition promotes TTF1-dependent redifferentiation and restores iodine uptake in thyroid carcinoma cell lines.

Theo S Plantinga, Bas Heinhuis, Danny Gerrits, Mihai G Netea, Leo A B Joosten, Ad R M M Hermus, Wim J G Oyen, Rebecca E Schweppe, Bryan R Haugen, Otto C Boerman and 2 more

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In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Defining theThyroid : official journal of the American Thyroid Association · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. 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 · 2021
    Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Two distinct E3 ligases, SCFFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  19. Personalized treatment options for thyroid cancer: current perspectives.Pharmacogenomics and personalized medicine · 2019
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Theo S PlantingaDepartments of Internal Medicine (T.S.P., B.H., M.G.N., L.A.B.J., A.R.M.M.H., J.W.A.S., R.T.N.-M.) and Nuclear Medicine (D.G., W.J.G.O., O.C.B.) and Division of Endocrinology (T.S.P., A.R.M.M.H., J.W.A.S., R.T.N.-M.), Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands; and Division of Endocrinology, Diabetes, and Metabolism (R.E.S., B.R.H.), University of Colorado Denver, Aurora, Colorado 80045.
Bas Heinhuis
Danny Gerrits
Mihai G Netea
Leo A B Joosten
Ad R M M Hermus
Wim J G Oyen
Rebecca E Schweppe
Bryan R Haugen
Otto C Boerman
Johannes W A Smit
Romana T Netea-Maier

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
TXNIP as a Key Regulator of Thyroid Cancer Metabolism and AggressivenessR01CA175994 · NCI · UNIVERSITY OF COLORADO DENVER · PI HAUGEN, BRYAN R. · 2013 to 2017
$1.6M
NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA175994
6 · The paper itself

Abstract

conceptRedifferentiation of thyroid carcinoma cells has the potential to increase the efficacy of radioactive iodine therapy in treatment-refractory, nonmedullary thyroid carcinoma (TC), leading to an improved disease outcome. Mammalian target of rapamycin (mTOR) is a key regulator of cell fate affecting survival and differentiation, with autophagy and inflammation as prominent downstream pathways.

methodsThe effects of mTOR inhibition were studied for its redifferentiation potential of the human TC cell lines BC-PAP, FTC133, and TPC1 by assessment of mRNA and protein expression of thyroid-specific genes and by performance of iodine uptake assays.

resultsIn thyroid transcription factor 1 (TTF1)-expressing cell lines, mTOR inhibition promoted redifferentiation of TC cells by the up-regulation of human sodium-iodine symporter mRNA and protein expression. Furthermore, these cells exhibited markedly elevated iodine uptake capacity. Surprisingly, this redifferentiation process was not mediated by autophagy induced during mTOR inhibition or by inflammatory mediators but through transcriptional effects at the level of TTF1 expression. Accordingly, small interfering RNA inhibition of TTF1 completely abrogated the induction of human sodium-iodine symporter by mTOR inhibition.

conclusionThe present study has identified the TTF1-dependent molecular mechanisms through which the inhibition of mTOR leads to the redifferentiation of TC cells and subsequently to increased radioactive iodine uptake.

Indexed as

AutophagyCarcinoma, Papillary, FollicularCell DifferentiationCell Line, TumorDNA-Binding ProteinsGene Expression Regulation, NeoplasticHumansInflammationInterleukin-6Iodine RadioisotopesSirolimusThyroid NeoplasmsTOR Serine-Threonine KinasesTranscription FactorsDNA-Binding ProteinsInterleukin-6Iodine RadioisotopesMTOR protein, humanSirolimusTOR Serine-Threonine KinasesTranscription FactorsTTF1 protein, human

Identifiers

PMID24712572
PMCPMC5393487

What OpenQuestion holds

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Registered trials

None linked

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.