Evidence map›Paper›PMID 39905539›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

Targeting CXCL8 signaling sensitizes HNSCC to anlotinib by reducing tumor-associated macrophage-derived CLU.

Xin Hu, Yikang Ji, Mi Zhang, Zhihui Li, Xinhua Pan, Zhen Zhang, Xu Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. 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

7 authors.

Xin Hu *Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Yikang Ji *Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Mi ZhangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Zhihui LiDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Xinhua PanDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Zhen ZhangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. 320056@sh9hospital.org.cn.
Xu WangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. wangx312016@sh9hospital.org.cn.ORCID http://orcid.org/0000-0001-9064-2434

Funding

National Natural Science Foundation of China 82073384National Natural Science Foundation of China 82272815
6 · The paper itself

Abstract

backgroundAlthough nutrition-starvation therapy for malignancies such as HNSCC is highly desirable, the clinical outcomes remain disappointing. Understanding the spatial heterogeneity of glucose deficiency can reveal the molecular mechanisms regulating cancer metabolism and identify therapeutic targets to improve effective nutrient-starvation therapies.

methodsMultiple omics data from RNA-seq, proteomics and spatial transcriptome analyses of HNSCC samples were integrated to analyze the spatial heterogeneity of glucose deficiency. In vivo and in vitro CXCL8 and CLU expression levels in tumor cells were determined using qPCR, immunohistochemistry and ELISA. The ability of CLU from TAMs to respond to tumor-derived CXCL8 was assessed using RNA sequencing, siRNA silencing, immunofluorescence and CCK-8 assays. A mouse subcutaneous xenograft model was used to assess the outcomes of nutrition-starvation therapy combined with blockade of CXCL8 signaling.

resultsA set of genes that was significantly upregulated in HNSCC under conditions of glucose deficiency was identified using integrating multiple omics data analyses. The upregulated gene set was used to determine the glucose-deficient area according to transcriptome data of HNSCC, and CXCL8 was one of the most highly upregulated genes. The levels of both CXCL8 mRNA and its protein IL-8 in cancer cells under conditions of glucose deficiency were increased in an NF-κB-dependent manner. Supplementary IL-8 stimulated TAMs to synthesize CLU, and CLU counteracted oxidative stress in HNSCC cells under conditions of glucose deficiency. Moreover, pharmacological blockade of CXCL8 signaling (reparixin) sensitized HNSCC cells to nutrient-starvation therapy (anlotinib) in two xenograft models.

conclusionOur results provide novel evidence of a feedback loop between cancer cells and TAMs in glucose-deficient regions. HNSCC-derived CXCL8 favors endogenous antioxidative processes and confers therapeutic resistance to nutrient-starvation therapies in HNSCC.

Indexed as

ClusterinHead and Neck NeoplasmsIndolesInterleukin-8Squamous Cell Carcinoma of Head and NeckAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceMice, NudeSignal TransductionXenograft Model Antitumor AssaysCLU protein, humanClusterinCXCL8 protein, humanIndolesInterleukin-8CLUCXCL8HNSCCNutrition starvationOxidative stress

Identifiers

PMID39905539
PMCPMC11796229

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.