Evidence map›Paper›PMID 41276817›Full record

ArticleCell communication and signaling : CCS2025

Fusobacterium nucleatum-reprogrammed adipocytes promote tumor cisplatin resistance through the CCL2-CCR2 axis in the necrotic metastatic neck nodes of head and neck carcinoma.

Feiran Li, Xiaohui Yuan, Hui-Ching Lau, Yi Zhu, Hongli Gong, Huiying Huang, Chi-Yao Hsueh, Ming Zhang

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 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

8 authors.

Feiran LiENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, China.
Xiaohui YuanENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, China.
Hui-Ching LauENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, China.
Yi ZhuDepartment of Radiation Oncology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, China.
Hongli GongENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, China.
Huiying HuangENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, China. huangjgcy@163.com.
Chi-Yao HsuehENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, China. hsuehchiyao@gmail.com.
Ming ZhangENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, China. ent_zhm@126.com.

Funding

National Natural Science Foundation of China 82203727National Natural Science Foundation of China 82273097Natural Science Foundation of Shanghai 23ZR1409700Shanghai Municipal Key Clinical Specialty shslczdzk00801Shanghai Sailing Program 22YF1405700
6 · The paper itself

Abstract

backgroundNecrosis plays a pivotal role in the development of cisplatin resistance in metastatic neck lymph nodes of head and neck squamous cell carcinoma (HNSCC). However, the precise mechanisms underlying this association remain unclear.

methodsWe employed qPCR and DNA in situ hybridization to detect Fusobacterium nucleatum (F. nucleatum) in postoperative tissue specimens from node-positive HNSCC patients. Transcriptomic sequencing was performed to analyze gene expression changes in adipocytes following F. nucleatum co-culture. RNA and protein expression alterations were validated via qPCR, Western blot, and ELISA. Additionally, subcutaneous xenograft tumor models were utilized for in vivo validation.

resultsF. nucleatum was found to preferentially colonize necrotic neck lymph nodes in HNSCC and infiltrate adjacent adipocytes. In vitro, F. nucleatum induced the formation of cancer-associated adipocytes via autocrine C-C motif chemokine ligand 2 (CCL2), which stimulated lipolysis and enhanced free fatty acid release. Paracrine CCL2 further drove glutathione accumulation and cisplatin resistance in HNSCC by upregulating solute carrier family 1 member 5 (SLC1A5) and solute carrier family 7 member 11 (SLC7A11). Notably, C-C chemokine receptor type 2 (CCR2) antagonist, RS504393, effectively reversed these F. nucleatum-mediated pro-tumor effects. In vivo studies further confirmed the role of F. nucleatum-reprogrammed adipocytes and the therapeutic potential of RS504393.

conclusionThis study is the first to elucidate the crucial involvement of F. nucleatum in shaping cancer-associated adipocytes within the HNSCC microenvironment. F. nucleatum-reprogrammed adipocytes enhance cisplatin resistance via the CCL2-CCR2 axis, offering new therapeutic avenues to overcome chemotherapy resistance in necrotic neck lymph nodes.

Indexed as

AdipocytesChemokine CCL2CisplatinDrug Resistance, NeoplasmFusobacterium nucleatumHead and Neck NeoplasmsReceptors, CCR2Squamous Cell Carcinoma of Head and NeckAnimalsCell Line, TumorHumansLymphatic MetastasisLymph NodesMaleMiceMice, NudeCCL2 protein, humanCCR2 protein, humanChemokine CCL2CisplatinReceptors, CCR2AdipocyteCCL2CisplatinFusobacterium nucleatumHead and neck carcinoma

Identifiers

PMID41276817
PMCPMC12750780

What Socratic 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 Socratic graph.