Evidence map›Paper›PMID 41580014›Full record

ArticleCancer letters2026

NR4A2 induces perineural invasion in head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma via CXCL5/CXCR2 signaling axis.

Sanjib Chaudhary, Muthamil Iniyan Appadurai, Koelina Ganguly, Ramesh Pothuraju, Han-Jun Wang, Jesse L Cox, Subodh M Lele, Mohd Wasim Nasser, Imayavaramban Lakshmanan, Muzafar A Macha and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2026. 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. Single-Cell Pan-Cancer Atlas Reveals GPR171 as a Candidate Marker of CD8International journal of molecular sciences · 2026
    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

12 authors.

Sanjib ChaudharyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Muthamil Iniyan AppaduraiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Koelina GangulyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Ramesh PothurajuDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Han-Jun WangDepartment of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Jesse L CoxDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Subodh M LeleDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Mohd Wasim NasserDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Imayavaramban LakshmananDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Muzafar A MachaWatson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Jammu and Kashmir, 192122, India. Electronic address: muzafar.aiiims@gmail.com.
Surinder Kumar BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: sbatra@unmc.edu.
Apar Kishor GantiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Division of Oncology-Hematology, VA Nebraska Western Iowa Health Care System, Omaha, NE, 68105, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Division of Oncology-Hematology, University of Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: aganti@unmc.edu.

Funding

Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI THAYER, SARAH P · 2018 to 2022
$8.1M
Modulation of Tumor Microenvironment for Improved Therapy of Pancreatic CancerR01CA247471 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., JAIN, MANEESH · 2020 to 2024
$2.8M
Novel approach to attenuate small cell lung cancer growth and metastasisR01CA218545 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI NASSER, MOHD WASIM · 2018 to 2022
$2.6M
Targeting MUC5AC mucin in breast cancer brain metastasisR01CA241752 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI NASSER, MOHD WASIM · 2021 to 2025
$2.3M
Targeted Radiation Therapy for Pancreatic CancerR01CA195586 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., JAIN, MANEESH · 2015 to 2019
$2.2M
Role of PD2/Paf1 in Pancreatic Acinar to Ductal MetaplasiaR01CA210637 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2017 to 2021
$2.0M
Rac1 GTPase in tumorigenesis and progression of pancreatic cancerR01CA206444 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., OUELLETTE, MICHEL M · 2016 to 2020
$1.9M
ST6GalNAc-I/MUC5AC promoting angiogenesis in lung adenocarcinomaR21CA267582 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI LAKSHMANAN, IMAYAVARAMBAN · 2022 to 2023
$387k
BLRD VA I01 BX004676NCI NIH HHS P01 CA217798NCI NIH HHS R01 CA195586NCI NIH HHS R01 CA206444NCI NIH HHS R01 CA210637NCI NIH HHS R01 CA218545NCI NIH HHS R01 CA241752NCI NIH HHS R01 CA247471NCI NIH HHS R21 CA267582
6 · The paper itself

Abstract

Perineural invasion (PNI) is associated with worse prognosis in various malignancies. Targeting PNI may hinder the tumor metastasis in head and neck squamous cell carcinoma (HNSCC) and pancreatic ductal adenocarcinoma (PDAC). We investigated the role of nuclear receptor subfamily 4 group A2 (NR4A2/Nurr1) mediated neuronal invasion in HNSCC and PDAC tumor progression. Aberrant expression of NR4A2 was observed in these tumors, and high levels of NR4A2 were associated with worse survival. The whole genome chromatin immunoprecipitation (ChIP) sequencing with NR4A2 antibody illustrated several genes associated with axonal guidance, suggesting its potential role in PNI. Treatment with conditioned-media (CM) collected from NR4A2-depleted cancer cells showed significantly decreased neurite outgrowths in dorsal root ganglion. Cytokine array analysis revealed several soluble factors, such as CXCL5, CCL2, IGBP2, and TIMP-2, that may be involved in neuritogenesis; these factors are decreased in CM of NR4A2-depleted cells. Further treatment with CXCL5 ligand significantly induced neuritogenesis, while the neurite outgrowth was abrogated when cotreated with CXCR2 (receptor for CXCL5) inhibitor SCH527123. Upregulation of Rac1 and phospho-AKT (S473) downstream signaling of CXCL5 was observed, and the CXCR2 inhibitor abrogated this effect in neuronal cells. Moreover, CM from CXCL5-depleted cells showed reduced neurite length. NR4A2 knockdown in UMSCC1 cells impaired tumor formation in vivo, and the xenograft tissues exhibited significant downregulation of CXCL5, providing direct in vivo evidence for the NR4A2-CXCL5 axis in tumor progression. NR4A2 is a key driver of CXCL5-mediated PNI and the NR4A2/CXCL5/CXCR2 signaling axis is a potential therapeutic target in HNSCC and PDAC.

Indexed as

Carcinoma, Pancreatic DuctalChemokine CXCL5Head and Neck NeoplasmsNuclear Receptor Subfamily 4, Group A, Member 2Pancreatic NeoplasmsReceptors, Interleukin-8BSquamous Cell Carcinoma of Head and NeckAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceMice, NudeNeoplasm InvasivenessSignal TransductionChemokine CXCL5CXCL5 protein, humanNR4A2 protein, humanNuclear Receptor Subfamily 4, Group A, Member 2Receptors, Interleukin-8BCancer–nerve crosstalkCXCL5Head and neck cancerNeuritogenesisNR4A2Pancreatic cancerPerineural invasion

Identifiers

PMID41580014
PMCPMC13202600

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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.