Evidence map›Paper›PMID 41123701›Full record

ArticleJournal of molecular histology2025

TAK-242 inhibits toll-like receptor-4 signaling and attenuates cancer-associated muscle atrophy via the p38-C/EBPβ pathway.

Yongfei You, Zhouzhou Su, Haozheng Wang, Shanshan Liu, Jiayi Wang, Feng Qiu, Zhiqun Jiang, Jianxin Wang, Yong Li, Guohua Zhang

Erratum issuedAbstract read
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In one paragraph

Article in Journal of molecular histology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Yongfei YouDepartment of Medical Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China.
Zhouzhou SuQueen Mary School of Nanchang University, Nanchang, 330036, Jiangxi Province, China.
Haozheng WangQueen Mary School of Nanchang University, Nanchang, 330036, Jiangxi Province, China.
Shanshan LiuQueen Mary School of Nanchang University, Nanchang, 330036, Jiangxi Province, China.
Jiayi WangQueen Mary School of Nanchang University, Nanchang, 330036, Jiangxi Province, China.
Feng QiuDepartment of Medical Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China.
Zhiqun JiangDepartment of Neurosurgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China.
Jianxin WangDepartment of Urology, Taizhou First People's Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, 318020, Zhejiang Province, China.
Yong LiDepartment of Medical Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China. liyong19_6@126.com.
Guohua ZhangDepartment of Medical Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China. zhanguohuazgh@126.com.

Funding

Nanchang Science and Technology Bureau of Jiangxi Province HONGKO Zi [2021] 156Nanchang Science and Technology Bureau of Jiangxi Province HONGKO Zi [2021] 200National Natural Science Foundation of China 82160493National Natural Science Foundation of China 82460592Natural Science Foundation of Jiangxi Province 20212BAB206081Natural Science Foundation of Jiangxi Province 20224ACB206018Zhejiang Province Basic Public Welfare Research Project LGF21H050001
6 · The paper itself

Abstract

BACKGROUND AND

aimsCancer cachexia is a paraneoplastic syndrome characterized by progressive muscle atrophy, which negatively impacts treatment efficacy, quality of life, and survival in individuals with cancer. Despite extensive research, no effective medical intervention has completely reversed cachexia, primarily due to an incomplete understanding of its pathogenesis. Toll-like receptor 4 (TLR4) plays an important role in inflammation and metabolic regulation. In this study, the role of TLR4 in muscle catabolism was investigated, with a focus on its regulation of the p38 mitogen-activated protein kinase (MAPK)-mediated activation of C/enhancer-binding protein beta (C/EBPβ) pathway.

methodsTLR4 expression was silenced in C2C12 myotubes using specific small interfering RNAs (siRNAs). Conditioned medium derived from various cancer cell types was applied to C2C12 myotubes to simulate the tumor microenvironment. The pharmacological TLR4 inhibitor TAK-242 was administrated to C2C12 myotubes and C26 tumor-bearing mice to evaluate its effects on muscle atrophy. Western blot analysis and immunofluorescence microscopy were performed on C2C12 myotubes, while muscle tissues from C26 tumor-bearing mice, a model of cancer cachexia, were analyzed using western blot and histological examination.

resultsExposure to conditioned medium from cachexia-associated cancer cell lines induced p38 MAPK-C/EBPβ in C2C12 myotubes, leading to upregulation of Ubr2 and Atrogin-1, myosin heavy chain degradation, and myotube atrophy. Silencing or inhibition of TLR4 using siRNA or TAK-242 prevented these catabolic effects in vitro. In C26 tumor-bearing mice, TAK-242 administration significantly attenuated cancer-associated muscle atrophy.

conclusionsTLR4 plays a critical role in cancer-associated muscle atrophy through the p38β MAPK-C/EBPβ signaling pathway in both in vitro and in vivo models. Pharmacological inhibition of TLR4 with TAK-242 effectively attenuated muscle atrophy, highlighting its potential therapeutic value.

Indexed as

CCAAT-Enhancer-Binding Protein-betaMuscular AtrophyNeoplasmsp38 Mitogen-Activated Protein KinasesSignal TransductionSulfonamidesToll-Like Receptor 4AnimalsCachexiaCell Line, TumorHumansMaleMiceMuscle Fibers, SkeletalCCAAT-Enhancer-Binding Protein-betaethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylatep38 Mitogen-Activated Protein KinasesSulfonamidesTlr4 protein, mouseToll-Like Receptor 4Cancer cachexiaMuscle wastingp38 MAPKTAK242TLR4

Identifiers

PMID41123701

What OpenQuestion holds

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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 OpenQuestion graph.