Evidence map›Paper›PMID 41057308›Full record

ArticleCell death & disease2025

HMGB1 orchestrates tumor-osteoclast crosstalk to drive bone metastasis in hepatocellular carcinoma.

Yan-Zhu Chen, Di Xu, Ya-Xun Jia, Jie Ma, Zuo-Lin Xiang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 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. Review
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

5 authors.

Yan-Zhu ChenDepartment of Radiation Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID http://orcid.org/0000-0003-1003-3095
Di XuDepartment of Radiation Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Ya-Xun JiaDepartment of Radiation Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Jie MaDepartment of Radiation Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID http://orcid.org/0000-0002-3880-6136
Zuo-Lin XiangDepartment of Radiation Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. xiangzuolinmd@hotmail.com.ORCID http://orcid.org/0000-0002-5725-842X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bone metastasis in hepatocellular carcinoma (HCC) poses a significant clinical challenge, characterized by poor prognosis and severe skeletal complications. This study identifies the HMGB1/LCN2/JAK1/STAT3 axis as the central mechanism driving HCC bone metastasis through tumor-osteoclast crosstalk. High-mobility group box 1 (HMGB1) induces osteoclast activation and differentiation, promoting lipocalin-2 (LCN2) secretion by osteoclasts, which activates the JAK1/STAT3 pathway in HCC cells, forming a feedback loop that enhances osteolytic bone resorption and tumor dissemination. Integrated single-cell and bulk RNA sequencing reveal enriched osteoclast-related and pro-metastatic pathways in the tumor-bone microenvironment, while functional assays involving knockdown and overexpression demonstrate that modulating the HMGB1/LCN2/JAK1/STAT3 axis regulates osteoclast activity, tumor growth, and bone destruction in vitro and in vivo. These results suggest the HMGB1/LCN2/JAK1/STAT3 axis as a potential therapeutic target, offering a strategy to reduce skeletal damage and systemic tumor progression, thereby contributing to improved management of advanced HCC.

Indexed as

Bone NeoplasmsCarcinoma, HepatocellularHMGB1 ProteinLiver NeoplasmsOsteoclastsAnimalsCell Line, TumorHumansJanus Kinase 1Lipocalin-2MiceSignal TransductionSTAT3 Transcription FactorTumor MicroenvironmentHMGB1 ProteinHMGB1 protein, humanJAK1 protein, humanJanus Kinase 1LCN2 protein, humanLipocalin-2STAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID41057308
PMCPMC12504543

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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.