Evidence map›Paper›PMID 41298817›Full record

ArticleBritish journal of cancer2026

Crosstalk of NPY and TGFβ orchestrates the signaling to facilitate perineural invasion of oral squamous cell carcinoma.

Jing Bi, Ketong Liu, Yiru Luo, Yueqi Zhou, Zhengyan Liu, Junting Tao, Jinhui Wei, Marene Landstrom, Yabing Mu, Guangxiang Zang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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

10 authors.

Jing Bi *Liaoning Provincial Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical University, Shenyang City, P.R. China.
Ketong Liu *Liaoning Provincial Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical University, Shenyang City, P.R. China.
Yiru Luo *Liaoning Provincial Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical University, Shenyang City, P.R. China.
Yueqi ZhouLiaoning Provincial Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical University, Shenyang City, P.R. China.
Zhengyan LiuLiaoning Provincial Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical University, Shenyang City, P.R. China.
Junting TaoLiaoning Provincial Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical University, Shenyang City, P.R. China.
Jinhui WeiLiaoning Provincial Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical University, Shenyang City, P.R. China.
Marene LandstromDepartment of Medical Bioscience, Building 6M, Umeå University, Umeå, Sweden.ORCID http://orcid.org/0000-0001-6737-7230
Yabing MuDepartment of Medical Bioscience, Building 6M, Umeå University, Umeå, Sweden. yabing.mu@umu.se.ORCID http://orcid.org/0000-0003-3193-1425
Guangxiang ZangLiaoning Provincial Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical University, Shenyang City, P.R. China. gxzang@cmu.edu.cn.ORCID http://orcid.org/0000-0002-3081-4780

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82072998National Natural Science Foundation of China (National Science Foundation of China) 82173322
6 · The paper itself

Abstract

backgroundPerineural invasion (PNI) frequently occurs in oral squamous cell carcinoma (OSCC) and predicts poor prognosis. Although PNI is increasingly recognised as a process driven by tumour-nerve crosstalk, the underlying molecular mechanisms remain unclear. We investigated the role of sympathetic nerve-derived neuropeptide Y (NPY) and its receptor NPY1R in OSCC PNI.

methodsNPY/NPY1R expression was assessed in human OSCC tissues by immunostaining, qPCR, and TCGA data analysis. Functional studies using Cal27 and SCC9 cells included migration, invasion, and sphere assays. The causal role of NPY1R was tested by lentiviral knockdown/overexpression, validated in tongue orthotopic xenografts, and further examined by NPY1R pharmacological inhibition in vivo.

resultsNPY was enriched in the PNI microenvironment, and malignant OSCC expressed high NPY1R, particularly at invasive fronts. Mechanistically, NPY activated ERK and Smad2 via NPY1R, synergising with TGFβ signalling in tumour cells expressing TβRI. This crosstalk enhanced proliferation, invasion, and PNI in vivo. Importantly, NPY1R inhibition markedly reduced tumour growth, metastasis, and PNI.

conclusionsWe identify NPY-NPY1R-TGFβ crosstalk as a novel mechanism enabling OSCC to exploit neural signals for PNI, highlighting a promising therapeutic target to block neural invasion and improve patient outcomes.

Indexed as

Carcinoma, Squamous CellMouth NeoplasmsNeuropeptide YReceptors, Neuropeptide YTransforming Growth Factor betaAnimalsCell Line, TumorCell MovementCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, NudeNeoplasm InvasivenessNeuropeptide Yneuropeptide Y-Y1 receptorReceptors, Neuropeptide YSmad2 ProteinTransforming Growth Factor beta

Identifiers

PMID41298817
PMCPMC12852772

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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.