Evidence map›Paper›PMID 34258492›Full record

ArticleJournal of the Endocrine Society2021

Thyroid Hormone Receptor Beta Inhibits PI3K-Akt-mTOR Signaling Axis in Anaplastic Thyroid Cancer via Genomic Mechanisms.

Cole D Davidson, Eric L Bolf, Noelle E Gillis, Lauren M Cozzens, Jennifer A Tomczak, Frances E Carr

Open access · goldAbstract read
In one paragraph

Article in Journal of the Endocrine Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
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

17 citing papers in PubMed, 18 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Cole D DavidsonDepartment of Pharmacology, Larner College of Medicine, Burlington, Vermont 05405, USA.ORCID https://orcid.org/0000-0002-3582-2691
Eric L BolfDepartment of Pharmacology, Larner College of Medicine, Burlington, Vermont 05405, USA.ORCID https://orcid.org/0000-0003-2579-2692
Noelle E GillisDepartment of Pharmacology, Larner College of Medicine, Burlington, Vermont 05405, USA.ORCID https://orcid.org/0000-0002-0005-4194
Lauren M CozzensDepartment of Pharmacology, Larner College of Medicine, Burlington, Vermont 05405, USA.
Jennifer A TomczakDepartment of Pharmacology, Larner College of Medicine, Burlington, Vermont 05405, USA.
Frances E CarrDepartment of Pharmacology, Larner College of Medicine, Burlington, Vermont 05405, USA.ORCID https://orcid.org/0000-0001-7266-8788
University of Vermont · US

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
Understanding Factors Influencing COVID-19 Testing and Vaccination in Immigrant Low-income and Homeless Populations and Testing Targeted InterventionsU54GM115516 · NIGMS · MAINEHEALTH · PI Frances E. Carr · 2017 to 2026
$51.6M
Nuclear Receptor Regulation of Epigenetics in Endocrine-Related CancersF99CA245796 · NCI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI GILLIS, NOELLE ELIZABETH · 2019 to 2020
$67k
NCI NIH HHS F99 CA245796NCI NIH HHS P30 CA046934NIGMS NIH HHS U54 GM115516
6 · The paper itself

Abstract

Thyroid cancer is the most common endocrine malignancy, and the global incidence has increased rapidly over the past few decades. Anaplastic thyroid cancer (ATC) is highly aggressive, dedifferentiated, and patients have a median survival of fewer than 6 months. Oncogenic alterations in ATC include aberrant phosphoinositide 3 kinase (PI3K) signaling through receptor tyrosine kinase (RTK) amplification, loss of phosphoinositide phosphatase expression and function, and protein kinase B (Akt) amplification. Furthermore, the loss of expression of the tumor suppressor thyroid hormone receptor beta (TRβ) is strongly associated with ATC. TRβ is known to suppress PI3K in follicular thyroid cancer and breast cancer by binding to the PI3K regulatory subunit p85α. However, the role of TRβ in suppressing PI3K signaling in ATC is not completely delineated. Here we report that TRβ indeed suppresses PI3K signaling in ATC cell lines through unreported genomic mechanisms, including a decrease in RTK expression and an increase in phosphoinositide and Akt phosphatase expression. Furthermore, the reintroduction and activation of TRβ in ATC cell lines enables an increase in the efficacy of the competitive PI3K inhibitors LY294002 and buparlisib on cell viability, migration, and suppression of PI3K signaling. These findings not only uncover additional tumor suppressor mechanisms of TRβ but shed light on the implication of TRβ status and activation on inhibitor efficacy in ATC tumors.

Indexed as

anaplastic thyroid cancerPI3KPI3K inhibitorPI3K phosphatasereceptor tyrosine kinasethyroid hormone receptor

Identifiers

PMID34258492
PMCPMC8271203
OpenAlexW3172022826

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.