Evidence map›Paper›PMID 38693105›Full record

ArticleCell death & disease2024

Impact of the thyroid hormone T3 and its nuclear receptor TRα1 on colon cancer stem cell phenotypes and response to chemotherapies.

Maria Virginia Giolito, Serguei Bodoirat, Theo La Rosa, Mathieu Reslinger, Gabriela D A Guardia, Jana Mourtada, Leo Claret, Alain Joung, Pedro A F Galante, Luiz O F Penalva and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. 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

11 authors at 4 institutions in 4 countries.

Maria Virginia GiolitoUniversité de Strasbourg, INSERM, IRFAC/UMR-S1113, FMTS, 67200, Strasbourg, France.ORCID 0000-0002-4888-7857
Serguei BodoiratUniversité de Strasbourg, INSERM, IRFAC/UMR-S1113, FMTS, 67200, Strasbourg, France.
Theo La RosaStem-Cell and Brain Research Institute, U1208 INSERM, USC1361 INRA, 69675, Bron, France.
Mathieu ReslingerUniversité de Strasbourg, INSERM, IRFAC/UMR-S1113, FMTS, 67200, Strasbourg, France.
Gabriela D A GuardiaCentro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, Brazil.
Jana MourtadaUniversité de Strasbourg, INSERM, IRFAC/UMR-S1113, FMTS, 67200, Strasbourg, France.
Leo ClaretUniversité de Strasbourg, INSERM, IRFAC/UMR-S1113, FMTS, 67200, Strasbourg, France.
Alain JoungUniversité de Strasbourg, INSERM, IRFAC/UMR-S1113, FMTS, 67200, Strasbourg, France.
Pedro A F GalanteCentro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, Brazil.
Luiz O F PenalvaGreehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0003-4491-6769
Michelina PlaterotiUniversité de Strasbourg, INSERM, IRFAC/UMR-S1113, FMTS, 67200, Strasbourg, France. michelina.plateroti@igbmc.fr.ORCID 0000-0003-0644-8837
Inserm · FRCentre National de la Recherche Scientifique · FRHospital Sírio-Libanês · BRThe University of Texas Health Science Center at San Antonio · US

Funding

Fondation pour la Recherche Médicale (Foundation for Medical Research in France) DEQ20181039598Institut National Du Cancer (French National Cancer Institute) PLBIO19-289Ligue Contre le Cancer 01X.2021
6 · The paper itself

Abstract

Colorectal cancers (CRCs) are highly heterogeneous and show a hierarchical organization, with cancer stem cells (CSCs) responsible for tumor development, maintenance, and drug resistance. Our previous studies showed the importance of thyroid hormone-dependent signaling on intestinal tumor development and progression through action on stem cells. These results have a translational value, given that the thyroid hormone nuclear receptor TRα1 is upregulated in human CRCs, including in the molecular subtypes associated with CSC features. We used an established spheroid model generated from the human colon adenocarcinoma cell line Caco2 to study the effects of T3 and TRα1 on spheroid formation, growth, and response to conventional chemotherapies. Our results show that T3 treatment and/or increased TRα1 expression in spheroids impaired the response to FOLFIRI and conferred a survival advantage. This was achieved by stimulating drug detoxification pathways and increasing ALDH1A1-expressing cells, including CSCs, within spheroids. These results suggest that clinical evaluation of the thyroid axis and assessing TRα1 levels in CRCs could help to select optimal therapeutic regimens for patients with CRC. Proposed mechanism of action of T3/TRα1 in colon cancer spheroids. In the control condition, TRα1 participates in maintaining homeostatic cell conditions. The presence of T3 in the culture medium activates TRα1 action on target genes, including the drug efflux pumps ABCG2 and ABCB1. In the case of chemotherapy FOLFIRI, the increased expression of ABC transcripts and proteins induced by T3 treatment is responsible for the augmented efflux of 5-FU and Irinotecan from the cancer cells. Taken together, these mechanisms contribute to the decreased efficacy of the chemotherapy and allow cells to escape the treatment. Created with BioRender.com .

Indexed as

Colonic NeoplasmsFluorouracilNeoplastic Stem CellsSpheroids, CellularThyroid Hormone Receptors alphaTriiodothyronineAldehyde Dehydrogenase 1 FamilyAntineoplastic Combined Chemotherapy ProtocolsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2Caco-2 CellsCamptothecinDrug Resistance, NeoplasmHumansLeucovorinPhenotypeAldehyde Dehydrogenase 1 FamilyALDH1A1 protein, humanATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2CamptothecinFluorouracilLeucovorinRetinal DehydrogenaseThyroid Hormone Receptors alphaTriiodothyronine

Identifiers

PMID38693105
PMCPMC11063186
OpenAlexW4396546409

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.