Evidence map›Paper›PMID 38418798›Full record

ArticleJournal of cancer research and clinical oncology2024

Role of hydroxymethylglutharyl-coenzyme A reductase in the induction of stem-like states in breast cancer.

María Paula Marks, Carla Alejandra Giménez, Luciana Isaja, Mariana Belén Vera, Francisco Raúl Borzone, Federico Pereyra-Bonnet, Leonardo Romorini, Guillermo Agustín Videla-Richardson, Norma Alejandra Chasseing, Juan Carlos Calvo and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of cancer research and clinical oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

6 citing papers in PubMed, 10 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

11 authors at 3 institutions in 2 countries.

María Paula MarksLaboratorio de Células Madre/Stem Cells Lab (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, CP 1428, Ciudad Autónoma de Buenos Aires, Argentina.
Carla Alejandra GiménezInstituto de Ciencias Básicas y Medicina Experimental, Instituto Universitario del Hospital Italiano, Potosí 4265, C1199ACL, Buenos Aires, Argentina.
Luciana IsajaLaboratorio de Investigación Aplicada a Las Neurociencias (LIAN), Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia (FLENI), Ruta 9, Km 53, B1625, Buenos Aires, Escobar, Argentina.
Mariana Belén VeraLaboratorio de Investigación Aplicada a Las Neurociencias (LIAN), Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia (FLENI), Ruta 9, Km 53, B1625, Buenos Aires, Escobar, Argentina.
Francisco Raúl BorzoneLaboratorio de Células Madre/Stem Cells Lab (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, CP 1428, Ciudad Autónoma de Buenos Aires, Argentina.
Federico Pereyra-BonnetInstituto de Ciencias Básicas y Medicina Experimental, Instituto Universitario del Hospital Italiano, Potosí 4265, C1199ACL, Buenos Aires, Argentina.
Leonardo RomoriniLaboratorio de Investigación Aplicada a Las Neurociencias (LIAN), Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia (FLENI), Ruta 9, Km 53, B1625, Buenos Aires, Escobar, Argentina.
Guillermo Agustín Videla-RichardsonLaboratorio de Investigación Aplicada a Las Neurociencias (LIAN), Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia (FLENI), Ruta 9, Km 53, B1625, Buenos Aires, Escobar, Argentina.
Norma Alejandra ChasseingLaboratorio de Células Madre/Stem Cells Lab (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, CP 1428, Ciudad Autónoma de Buenos Aires, Argentina.
Juan Carlos CalvoLaboratorio de Células Madre/Stem Cells Lab (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, CP 1428, Ciudad Autónoma de Buenos Aires, Argentina.
Luciano VellónLaboratorio de Células Madre/Stem Cells Lab (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, CP 1428, Ciudad Autónoma de Buenos Aires, Argentina. luciano.vellon@ibyme.conicet.gov.ar.ORCID http://orcid.org/0000-0001-8531-6503
Consejo Nacional de Investigaciones Científicas y Técnicas · ARFundación para la Lucha contra las Enfermedades Neurológicas de la Infancia · ARInis Biotech (Argentina) · AR

Funding

National Research Council PIP300, 2014-2016, Argentina
6 · The paper itself

Abstract

purposeDe novo synthesis of cholesterol and its rate-limiting enzyme, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR), is deregulated in tumors and critical for tumor cell survival and proliferation. However, the role of HMGCR in the induction and maintenance of stem-like states in tumors remains unclear.

methodsA compiled public database from breast cancer (BC) patients was analyzed with the web application SurvExpress. Cell Miner was used for the analysis of HMGCR expression and statin sensitivity of the NCI-60 cell lines panel. A CRISPRon system was used to induce HMGCR overexpression in the luminal BC cell line MCF-7 and a lentiviral pLM-OSKM system for the reprogramming of MCF-7 cells. Comparisons were performed by two-tailed unpaired t-test for two groups and one- or two-way ANOVA.

resultsData from BC patients showed that high expression of several members of the cholesterol synthesis pathway were associated with lower recurrence-free survival, particularly in hormone-receptor-positive BC. In silico and in vitro analysis showed that HMGCR is expressed in several BC cancer cell lines, which exhibit a subtype-dependent response to statins in silico and in vitro. A stem-like phenotype was demonstrated upon HMGCR expression in MCF-7 cells, characterized by expression of the pluripotency markers NANOG, SOX2, increased CD44 +/CD24low/ -, CD133 + populations, and increased mammosphere formation ability. Pluripotent and cancer stem cell lines showed high expression of HMGCR, whereas cell reprogramming of MCF-7 cells did not increase HMGCR expression.

conclusionHMGCR induces a stem-like phenotype in BC cells of epithelial nature, thus affecting tumor initiation, progression and statin sensitivity.

Indexed as

Breast NeoplasmsHydroxymethylglutaryl-CoA Reductase InhibitorsCholesterolFemaleHumansHydroxymethylglutaryl CoA ReductasesOxidoreductasesCholesterolHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl CoA ReductasesOxidoreductasesBreast cancerCancer stem cellsHMGCRMetabolic reprogramming

Identifiers

PMID38418798
PMCPMC10902018
OpenAlexW4392242951

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.