Evidence map›Paper›PMID 41315933›Full record

ArticleCellular & molecular biology letters2025

CUEDC1 promotes glycolytic metabolism reprogramming through the CUEDC1/CACNG4/PI3K axis to promote ER-positive breast cancer growth.

Zexiu Lu, Ming Lei, Jian Chen, Ao Deng, Chao Chang, Jing Chen, Die Meng, Rui Wang, Xueying Wan, Gang Tu and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular & molecular biology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Zexiu Lu *Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Ming Lei *Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Jian Chen *Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Ao DengDepartment of Breast and Thyroid Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Chao ChangKey Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
Jing ChenKey Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
Die MengKey Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
Rui WangKey Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
Xueying WanKey Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
Gang TuDepartment of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Manran LiuDepartment of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. manranliu@cqmu.edu.cn.
Lingfeng TangDepartment of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. telephoneme@sina.com.ORCID http://orcid.org/0000-0002-5507-386X

Funding

Clinical College Clinical Medicine first-class discipline construction project to department of Breast and Thyroid Surgery CYYY-BSYJSCXXW-202322the Outstanding Professorship Program of Chongqing Medical University 2019-R10005
6 · The paper itself

Abstract

backgroundThe reprogramming of energy metabolism, particularly glycolysis, upholds the malignancy of tumors. The relationship between CUE domain-containing protein-1 (CUEDC1) and glycolysis, along with its influence on the development of estrogen receptor-positive breast cancer (ER+ BRCA), is not well defined. This investigation explores the functional involvement of CUEDC1 in glycolysis regulation and uncovers a previously unidentified pathway contributing to the progression of ER+ BRCA.

methodsImmunohistochemistry, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of CUEDC1 in ER+ BRCA tissues and cell lines. A series of molecular analyses, including dual-luciferase reporter assays, RNA-seq, and chromatin immunoprecipitation (ChIP), were performed to elucidate the potential mechanisms underlying CUEDC1’s involvement in ER+ BRCA progression. Metabolic assays focusing on glycolysis were employed to investigate the functional roles of CUEDC1 and calcium voltage-gated channel auxiliary subunit gamma 4 (CACNG4). The Connectivity Map (CMap) database was utilized to screen CUEDC1 inhibitors.

resultsCUEDC1 is aberrantly upregulated in ER+ BRCA tissues and cells. Increased CUEDC1 can promote enhanced tumor growth and lead to poor clinical outcomes in patients with ER+ BRCA. The MYC associated zinc finger protein (MAZ) can upregulate CUEDC1 gene transcription in ER+ BRCA cells by directly binding to its promoter. We determined that CUEDC1 directly modulated CACNG4 to enhance phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway activation, thereby facilitating tumor growth of ER+ BRCA. Clinical observations also revealed a positive correlation between CACNG4 expression and CUEDC1, with both factors being strongly associated with poor prognosis in patients with ER+ BRCA. Mechanistically, The CUEDC1/CACNG4/PI3K signal axis enhanced glycolysis through upregulating glucose transporter 1 (GLUT1), a crucial protein in glucose metabolism, thereby supporting tumor growth of ER+ BRCA. Furthermore, methotrexate was identified as a potential inhibitor of CUEDC1. Importantly, the combination of ipatasertib (a PI3K/AKT pathway inhibitor), with methotrexate effectively suppressed growth of ER+ BRCA in a mouse model.

conclusionsOur research reveals that enhanced CUEDC1 plays an essential role to ER+ BRCA cell proliferation and tumor growth via the CACNG4/PI3K axis. CUEDC1 is a promising prognostic factor of ER+ BRCA, and the CUEDC1/CACNG4/PI3K axis can serve as a potential therapeutic target for ER+ BRCA treatment.

Indexed as

Breast NeoplasmsGlycolysisMembrane ProteinsPhosphatidylinositol 3-KinasesReceptors, EstrogenAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingMiceSignal TransductionMembrane ProteinsPhosphatidylinositol 3-KinasesReceptors, EstrogenCACNG4CUEDC1ER-positive breast cancerGlycolysis

Identifiers

PMID41315933
PMCPMC12664147

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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.