Evidence map›Paper›PMID 35589690›Full record

ArticleCell death & disease2022

Cancer associated fibroblast-derived CCL5 promotes hepatocellular carcinoma metastasis through activating HIF1α/ZEB1 axis.

Haixu Xu, Jie Zhao, Jinping Li, Zhifeng Zhu, Zhaohai Cui, Ran Liu, Rong Lu, Zhi Yao, Qiong Xu

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
12.9field-weighted citation impact, top 1% of its field
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

98 citing papers in PubMed, 123 citations in OpenAlex.

  1. Diagnostic performance of [European journal of nuclear medicine and molecular imaging · 2025
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  8. Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026
    Review
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  11. Targeting Tumor-Associated Macrophages and Cancer-Associated Fibroblasts to Overcome Therapeutic Resistance in Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
  12. Single-cell dissection of pleural and systemic immunity uncovers pathogen-specific immune reprogramming in tuberculosis versus lung adenocarcinoma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
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  15. Review
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38 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 1 country.

Haixu Xu *Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
Jie Zhao *Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
Jinping LiDepartment of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
Zhifeng ZhuDepartment of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
Zhaohai CuiDepartment of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
Ran LiuDepartment of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
Rong LuTianjin Kangzhe Pharmaceutical Technology Development Company, Ltd, 300042, Tianjin, China. lu_rong@vip.sina.com.
Zhi YaoDepartment of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China. yaozhi@tmu.edu.cn.ORCID 0000-0001-8472-0731
Qiong XuDepartment of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China. xvqiong1980@vip.sina.com.ORCID 0000-0002-8891-1807
Tianjin Medical University · CNTianjin Institute of Pharmaceutical Research (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAFs) are one of the most enriched components of Hepatocellular carcinoma (HCC) microenvironment, which are tightly related to the metastasis and invasion of HCC. We identified a mechanism by which CAF-derived chemokine CCL5 enhanced HCC metastasis by triggering the HIF1α/ZEB1 axis. We demonstrated that CAFs derived from HCC tissues promoted the migration and invasion of HCC cells and facilitated metastasis to the lung of NOD/SCID mice. Then the chemokine antibody array elucidated the higher chemokine CCL5 level secreted by CAFs than by paracancerous tissue fibroblasts (PTFs). Mechanistically, we found that CAF-derived CCL5 inhibited the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF1α) by binding to specific receptors, maintained HIF1α under normoxia, thereby up-regulated the downstream gene zinc finger enhancer-binding protein 1 (ZEB1) and induced epithelial-mesenchymal transition (EMT), ultimately validating its ability to promote lung metastasis of HCC. And this novel mechanism may have association with poor prognosis. Taken together, targeting CAF-derived CCL5 mediated HIF1α/ZEB1 cascade possibly propose a new therapeutic route for HCC.

Indexed as

Cancer-Associated FibroblastsCarcinoma, HepatocellularLiver NeoplasmsAnimalsCell Line, TumorCell MovementChemokine CCL5Epithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticMiceMice, Inbred NODMice, SCIDNeoplasm MetastasisTumor MicroenvironmentChemokine CCL5

Identifiers

PMID35589690
PMCPMC9119971
OpenAlexW4280517827

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.