Evidence map›Paper›PMID 39073190›Full record

ArticleCancer science2024

Blocking CXCR4-CARM1-YAP axis overcomes osteosarcoma doxorubicin resistance by suppressing aerobic glycolysis.

Zihua Li, Hengli Lu, Yiwei Zhang, Jiyang Lv, Yi Zhang, Tianyang Xu, Dong Yang, Zhengwei Duan, Yonghao Guan, Zongrui Jiang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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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

12 authors.

Zihua LiDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID https://orcid.org/0000-0002-6087-7459
Hengli LuDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Yiwei ZhangDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Jiyang LvState Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology and Immunology, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Yi ZhangDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Tianyang XuDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Dong YangDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhengwei DuanDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Yonghao GuanDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Zongrui JiangDepartment of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Kaiyuan LiuDepartment of Orthopedics, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Yuxin LiaoDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID https://orcid.org/0000-0002-6783-3707

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteosarcoma, recognized for its aggressiveness and resistance to chemotherapy, notably doxorubicin, poses significant treatment challenges. This comprehensive study investigated the CXCR4-CARM1-YAP signaling axis and its pivotal function in controlling aerobic glycolysis, which plays a crucial role in doxorubicin resistance. Detailed analysis of Dox-resistant 143b/MG63-DoxR cells has uncovered the overexpression of CXCR4. Utilizing a combination of molecular biology techniques including gene silencing, aerobic glycolysis assays such as Seahorse experiments, RNA sequencing, and immunofluorescence staining. The study provides insight into the mechanistic pathways involved. Results demonstrated that disrupting CXCR4 expression sensitizes cells to doxorubicin-induced apoptosis and alters glycolytic activity. Further RNA sequencing revealed that CARM1 modulated this effect through its influence on glycolysis, with immunofluorescence of clinical samples confirming the overexpression of CXCR4 and CARM1 in drug-resistant tumors. Chromatin immunoprecipitation studies further highlighted the role of CARM1, showing it to be regulated by methylation at the H3R17 site, which in turn affected YAP expression. Crucially, in vivo experiments illustrated that CARM1 overexpression could counteract the tumor growth suppression that resulted from CXCR4 inhibition. These insights revealed the intricate mechanisms at play in osteosarcoma resistance to doxorubicin and pointed toward potential new therapeutic strategies that could target this metabolic and signaling network to overcome drug resistance and improve patient outcomes.

Indexed as

Bone NeoplasmsDoxorubicinDrug Resistance, NeoplasmOsteosarcomaProtein-Arginine N-MethyltransferasesReceptors, CXCR4Transcription FactorsYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingAnimalsApoptosisCell Line, TumorGene Expression Regulation, NeoplasticGlycolysisHumansMiceAdaptor Proteins, Signal Transducingcoactivator-associated arginine methyltransferase 1CXCR4 protein, humanDoxorubicinProtein-Arginine N-MethyltransferasesReceptors, CXCR4Transcription FactorsYAP1 protein, humanYAP-Signaling Proteinsaerobic glycolysisCXCR4–CARM1–YAPdoxorubicinosteosarcomaresistance

Identifiers

PMID39073190
PMCPMC11447900

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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.