Evidence map›Paper›PMID 40619388›Full record

ArticleBreast cancer research : BCR2025

THEM6 modulates carboplatin sensitivity by regulating ferroptosis through FDFT1 in triple-negative breast cancer.

Yuexiang Zeng, Zhijie Xu, Juan Huang, Qiaoli Yi, Xi Chen, Jiayu Wang, Zhihao Du, Jian Tian, Yuanliang Yan

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Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

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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, 1 synthesis or guideline pooled it.

  1. Pooled it
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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

9 authors.

Yuexiang ZengDepartment of Anesthesiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China.
Zhijie XuDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Juan HuangDepartment of Breast Surgery, Multidisciplinary Breast Cancer Center, Xiangya Hospital, Clinical Research Center for Breast Cancer in Hunan Province, Central South University, Changsha, China.
Qiaoli YiDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Xi ChenDepartment of Pharmacy, The Hunan Institute of Pharmacy Practice and Clinical Research, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Jiayu WangDepartment of Pharmacy, The Hunan Institute of Pharmacy Practice and Clinical Research, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Zhihao DuDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Jian TianDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China. jian_tian@csu.edu.cn.
Yuanliang YanDepartment of Pharmacy, The Hunan Institute of Pharmacy Practice and Clinical Research, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. yanyuanliang@csu.edu.cn.

Funding

National Natural Sciences Foundation of China 82473299Natural Science Foundation of Hunan Province 2024JJ2092Natural Science Foundation of Hunan Province 2024JJ9133
6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis, as chemotherapy resistance leads to relapse in many patients. Carboplatin addition improves treatment response, but challenges persist.

methodsTo identify novel targets for TNBC, we analyzed differentially expressed proteins in patients treated with neoadjuvant chemotherapy. Cell viability was assessed using CCK-8 and colony formation assays. In vivo effects were studied in an orthotopic xenograft model using THEM6 overexpression cells. ROS, iron levels, MDA, and mitochondrial ultrastructure were assessed. Protein expression was analyzed by Western blotting and RT-PCR, and FDFT1 ubiquitination was evaluated.

resultsWe identified THEM6 (co-downregulated) and PGRMC1 (co-upregulated) as survival-associated proteins. THEM6 overexpression enhanced carboplatin sensitivity in vitro and in vivo, reducing tumor weight and volume. THEM6-induced sensitivity was linked to ferroptosis, as the ferroptosis inhibitor Fer-1 reversed the effect, while apoptosis, necrosis, and autophagy inhibitors had no impact. THEM6 overexpression reduced GPX4 and SLC7A11, while increasing ACSL4. TEM revealed mitochondrial damage, and iron, MDA, and ROS levels were elevated in treated cells. Mechanistically, THEM6 stabilized FDFT1 by inhibiting its K48-linked ubiquitination, prolonging its protein half-life, and promoting ferroptosis. FDFT1 knockdown reversed THEM6-induced sensitivity to carboplatin.

conclusionsOur findings suggest that THEM6 enhances carboplatin sensitivity in TNBC by promoting ferroptosis through regulation of FDFT1. THEM6 may serve as a novel therapeutic target to improve TNBC treatment outcomes.

Indexed as

CarboplatinDrug Resistance, NeoplasmFerroptosisMembrane ProteinsTriple Negative Breast NeoplasmsAnimalsAntineoplastic AgentsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudeReceptors, ProgesteroneXenograft Model Antitumor AssaysAntineoplastic AgentsCarboplatinMembrane ProteinsPGRMC1 protein, humanReceptors, ProgesteroneCarboplatinFDFT1FerroptosisTHEM6Triple-negative breast cancer

Identifiers

PMID40619388
PMCPMC12232811

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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 OpenQuestion graph.