Evidence map›Paper›PMID 42435251›Full record

ArticleApoptosis : an international journal on programmed cell death2026

Axitinib promotes stemness and vasculogenic mimicry in triple-negative breast cancer by disrupting THBS1-CD47 axis-mediated endothelial-tumor cell communication.

Lei Lei, Huanhuan Zhou, Xiaojing Lai, Zeng Wang, Rongguo Li, Chengyong Du, Xiangming He, Lingbin Du, Yabing Zheng, Xiaojia Wang and 1 more

Abstract read
In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Lei Lei *Department of Breast Medical Oncology, Zhejiang Cancer Hospital, No.1 Banshan East Road, Gongshu District, Hangzhou, 310022, Zhejiang, China.
Huanhuan Zhou *Department of Breast Medical Oncology, Zhejiang Cancer Hospital, No.1 Banshan East Road, Gongshu District, Hangzhou, 310022, Zhejiang, China.
Xiaojing LaiDepartment of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, China.
Zeng WangDepartment of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
Rongguo LiDepartment of Thyroid and Breast Surgery, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China.
Chengyong DuDepartment of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Xiangming HeDepartment of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
Lingbin DuZhejiang Provincial Office for Cancer Prevention and Control, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
Yabing ZhengDepartment of Breast Medical Oncology, Zhejiang Cancer Hospital, No.1 Banshan East Road, Gongshu District, Hangzhou, 310022, Zhejiang, China.
Xiaojia WangDepartment of Breast Medical Oncology, Zhejiang Cancer Hospital, No.1 Banshan East Road, Gongshu District, Hangzhou, 310022, Zhejiang, China. wxiaojia0803@163.com.ORCID 0000-0002-7005-0842
Xiying ShaoDepartment of Breast Medical Oncology, Zhejiang Cancer Hospital, No.1 Banshan East Road, Gongshu District, Hangzhou, 310022, Zhejiang, China. shaoxy@zjcc.org.cn.ORCID 0000-0001-6553-6824

Funding

Zhejiang Cancer Foundation of Scientific Research ZJCF-2025-1-YB-11Zhejiang Medical and Health Science and Technology Project 2022KY637
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options. Although anti-angiogenic agents like Axitinib are used in cancers, resistance emerges through poorly understood mechanisms involving stemness and vasculogenic mimicry (VM). Here, we investigated the regulatory role of thrombospondin-1 (THBS1), an anti-angiogenic protein, in Axitinib-mediated signaling and its impact on TNBC. The effects of Axitinib on VM, angiogenesis, and stemness in TNBC were investigated through in vivo models and in vitro endothelial-supernatant cultures. Bioinformatics analyses (GSE230643 and CellChat), immunohistochemistry of clinical samples, exosome transfer assays, and xenograft models were employed to explore how Axitinib regulates THBS1-mediated endothelial-TNBC intercellular communication. Further bioinformatics analyses, combined with in vitro and in vivo experimental validations, were performed to elucidate the mechanism of the THBS1-CD47 axis in TNBC. Axitinib treatment increased stemness and promoted VM in TNBC models, despite tumor growth inhibition. Bioinformatics analyses revealed the Axitinib-dependent THBS pathway between endothelial and endothelial-like tumor cells. Axitinib-induced downregulation of THBS1 expression in HUVEC cells promoted stemness and angiogenesis of recipient TNBC cells via exosomes. Mechanistically, endothelial-derived THBS1 promoted CD47 expression in recipient TNBC cells, thereby attenuating the activity of PI3K/Akt and MAPK/ERK signaling pathways, and inhibiting stemness, angiogenesis, and VM. Importantly, Axitinib disrupted this THBS1-CD47 axis by downregulating endothelial-derived THBS1 expression. Axitinib induces the suppression of THBS1 expression in endothelial cells, thereby enhancing stemness and VM in recipient TNBC via disruption of the THBS1-CD47 axis. Restoring THBS1 signaling may represent a promising strategy to overcome Axitinib resistance.

Indexed as

AxitinibCD47 AntigenCell CommunicationNeoplastic Stem CellsNeovascularization, PathologicThrombospondin 1Triple Negative Breast NeoplasmsAnimalsCell Line, TumorEndothelial CellsFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudeSignal TransductionAxitinibCD47 AntigenThrombospondin 1thrombospondin-1, humanAxitinib resistanceIntercellular communicationTHBS1Triple-negative breast cancerVasculogenic mimicry

Identifiers

PMID42435251
PMCPMC13356087

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.