Evidence map›Paper›PMID 41511661›Full record

ArticleApoptosis : an international journal on programmed cell death2026

Downregulation of NFIA facilitates glycolysis, histone lactylation, and activation of the FN1-integrin α5β1 pathway in pancreatic cancer.

Xi Zhang, Yang Liu, Xiaoming Liu, Juan Tan, Lehong Yuan, Weijie Wu, Xiaoyan Li, Pan Xi, Guoyin Li, Zewen Song

Abstract read
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In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 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. Article
  3. 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

10 authors.

Xi Zhang *Department of Oncology, The Third Xiangya Hospital of Central South University, Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 10013, Hunan, China.
Yang Liu *Department of Pathology, The Third Xiangya Hospital of Central South University, Central South University, Changsha, China.
Xiaoming Liu *Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Central South University, Changsha, China.
Juan TanDepartment of Pathology, The Third Xiangya Hospital of Central South University, Central South University, Changsha, China.
Lehong YuanDepartment of Emergency, The Third Xiangya Hospital of Central South University, Central South University, Changsha, China.
Weijie WuDepartment of Oncology, The Third Xiangya Hospital of Central South University, Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 10013, Hunan, China.
Xiaoyan LiDepartment of Blood Transfusion, Shanxi Provincial People's Hospital, Taiyuan, China.
Pan XiDepartment of Radiotherapy, Shaanxi Provincial Tumor Hospital, Xi'an, China.
Guoyin LiCollege of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, No. 6, Wenchang Road, Chuanhui District, Zhoukou, 466001, Henan, China. ligy@zknu.edu.cn.
Zewen SongDepartment of Oncology, The Third Xiangya Hospital of Central South University, Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 10013, Hunan, China. xy3songzw@csu.edu.cn.

Funding

National Natural Science Foundation of China 81802940Outstanding Youth Foundation of Hunan Province 2022JJ20092Wisdom Gathering and Talent Cultivating Program from the Third Xiangya Hospital YX202211Youth Research Project of Shanxi Natural Science Foundation 202303021212349
6 · The paper itself

Abstract

Pancreatic cancer (PC) is a lethal malignancy with limited therapeutic options, characterized by tumor suppressor loss and metabolic-stromal crosstalk. This study aimed to introduce nuclear factor I A (NFIA) as a key tumor suppressor whose downregulation in PC was correlated with advanced tumor stages and poor prognosis. Functionally, NFIA overexpression suppressed PC cell proliferation, migration, and invasion, whereas NFIA silencing exacerbated these malignant phenotypes. Mechanistically, NFIA directly repressed the transcription of the glycolytic enzyme PKM, thereby attenuating glucose uptake and lactate production. Lactate generated from NFIA deficiency-induced glycolysis promoted histone lactylation, which epigenetically upregulated fibronectin 1 (FN1) expression in both cancer cells and cancer-associated fibroblasts. Elevated FN1 activated the integrin α5β1-FAK-PI3K-Akt signaling axis, thereby fostering invasive and metastatic behavior. Furthermore, NFIA transcriptionally suppressed FN1 expression, establishing a dual regulatory mechanism that bridged metabolic reprogramming and extracellular matrix remodeling. Collectively, our study indicated NFIA as a key tumor suppressor of PC progression, orchestrating the crosstalk between glycolysis inhibition and FN1-integrin pathway inactivation. These findings position NFIA restoration as a therapeutic strategy to disrupt metabolic-stromal synergy in aggressive PC, offering insights into the epigenetic-metabolic interplay underlying tumor microenvironment evolution.

Indexed as

FibronectinsGlycolysisHistonesIntegrin alpha5beta1NFI Transcription FactorsPancreatic NeoplasmsAnimalsCell Line, TumorCell MovementCell ProliferationDown-RegulationGene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingSignal TransductionFibronectinsFN1 protein, humanHistonesIntegrin alpha5beta1NFI Transcription FactorsFN1GlycolysisHistone lactylationNFIAPancreatic cancer

Identifiers

PMID41511661

What Socratic holds

Textmetadata
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.