Evidence map›Paper›PMID 41844706›Full record

ArticleScientific reports2026

Kynurenine promotes angiogenesis through mTOR signaling in head and neck squamous cell carcinoma.

Shuoqi Lin, Tesen Liao, Shijie Wang, Genggeng Zheng, Bohua Su, Dali Zheng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

6 authors.

Shuoqi Lin *Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People's Republic of China.
Tesen Liao *Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People's Republic of China.
Shijie WangFujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People's Republic of China.
Genggeng ZhengFujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People's Republic of China.
Bohua SuFujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People's Republic of China. sudoctor2005@126.com.
Dali ZhengFujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People's Republic of China. dalizheng@fjmu.edu.cn.

Funding

National Natural Science Foundation of China 82173180the Natural Science Foundation of Fujian Province 2025J01142the Special Project of Central Government for Local Science and Technology Development of Fujian Province 2023L3011
6 · The paper itself

Abstract

Angiogenesis and its maturation play a crucial role in the progression and prognosis of head and neck squamous cell carcinoma (HNSCC). Tumor growth relies on an adequate blood supply to meet metabolic demands, while metabolic reprogramming within the tumor microenvironment actively reshapes vascular architecture. Meanwhile, the tumor microenvironment induces metabolic reprogramming that reshapes the vasculature. Alterations in tryptophan metabolism have been observed in HNSCC, with kynurenine (Kyn) significantly elevated in cancer tissues. Although Kyn has been reported to regulate vascular function in several diseases, its role in angiogenesis in HNSCC remains unclear. Metabolic profiling assessed alterations in tryptophan metabolism in HNSCC. Transcriptomic data from the TCGA HNSCC cohort were analyzed to examine correlations between IDO1 expression and angiogenesis-related genes. These findings were validated in tumor specimens from 28 HNSCC patients via immunohistochemistry. Based on these clinical observations, functional and mechanistic studies were conducted using human umbilical vein endothelial cells (HUVECs) and the chick embryo chorioallantoic membrane (CAM) model to evaluate the effects of Kyn on endothelial migration, angiogenic capacity, and neovascularization. A subcutaneous cell-derived xenograft (CDX) mouse model was further employed to assess the association between IDO1 expression and vascular markers in vivo. The involvement of IDO1-mediated Kyn production and mTOR signaling activation was further investigated. Tryptophan metabolism was markedly reprogrammed in HNSCC, with significantly elevated levels of Kyn in tumor tissues. Analysis of the TCGA HNSCC cohort revealed that IDO1, the key enzyme responsible for kynurenine production, was positively correlated with multiple angiogenesis-related genes. Immunohistochemical analysis revealed a positive correlation between IDO1 expression and endothelial markers CD31 and CD34 in patient samples, suggesting a potential link between Kyn and tumor angiogenesis. Consistently, Kyn enhanced endothelial cell migration and tube formation in vitro and promoted neovascularization in the CAM model. In line with these findings, analysis of tumor tissues from the CDX mouse model demonstrated positive correlations between IDO1 expression and multiple vascular markers, including CD31, CD34, and CD105. Mechanistically, IDO1-driven Kyn production activated the mTOR pathway in endothelial cells, leading to the upregulation of angiogenesis-related genes, pro-angiogenic factors, and their receptors. These findings reveal a novel pro-angiogenic role of Kyn in HNSCC, mediated through IDO1-dependent tryptophan metabolism and mTOR pathway activation. Targeting tryptophan metabolism may provide a potential therapeutic strategy for highly vascularized HNSCC.

Indexed as

Head and Neck NeoplasmsKynurenineNeovascularization, PathologicSignal TransductionSquamous Cell Carcinoma of Head and NeckTOR Serine-Threonine KinasesAnimalsCell Line, TumorCell MovementChick EmbryoFemaleGene Expression Regulation, NeoplasticHumansHuman Umbilical Vein Endothelial CellsIndoleamine-Pyrrole 2,3,-DioxygenaseMaleIDO1 protein, humanIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineMTOR protein, humanTOR Serine-Threonine KinasesTryptophanAngiogenesisHead and neck squamous cell carcinomaKynurenineMetabolic reprogrammingMTOR

Identifiers

PMID41844706
PMCPMC13129111

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.