Evidence map›Paper›PMID 41761234›Full record

ArticleJournal of experimental & clinical cancer research : CR2026

Mechanism of cancer-associated fibroblast-driven thyroid cancer dedifferentiation via the ZFP57-PKM2 axis-mediated lactate secretion and therapeutic intervention with resveratrol​.

Xiaoyu Ji, Chengzhou Lv, Xian Wu, Hongpeng Wu, Yuang Chang, Qi Liu, Wenwu Dong, Jiapeng Huang, Dalin Zhang, Yao Diao and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 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. 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

15 authors.

Xiaoyu Ji *Department of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Chengzhou Lv *Department of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Xian Wu *Department of Urology, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Hongpeng WuDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Yuang ChangDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Qi LiuDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Wenwu DongDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Jiapeng HuangDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Dalin ZhangDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Yao DiaoDepartment of Nuclear Medicine, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Dapeng SunDepartment of Hepatobiliary Surgery General Hospital of Northern Theater Command, No.83,Wenhua Road, Shenhe District, Shenyang, 110016, China.
Zhihong WangDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Ping ZhangDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
Wei SunDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China. sun19890208@126.com.
Hao ZhangDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China. haozhang@cmu.edu.cn.

Funding

Basic Research Project of Liaoning Provincial Department of Education LJKMZ20221175Liaoning Provincial Science and Technology Joint Program 2024-MSLH-558Liaoning Provincial Science and Technology Joint Program 2025-BSLH-390Liaoning Provincial Science and Technology Joint Program 2025-MSLH-737Natural Science Foundation of liaoning Proveince 2025-BS-0947Natural Science Foundation of Liaoning Province 2023-MS-156The Basic Scientific Research Project Plan for Higher Education Institutions of the Liaoning Provincial Department of Education LJ242410159046The Natural Science Foundation of Liaoning Province 2024-MS-054
6 · The paper itself

Abstract

Papillary thyroid carcinoma (PTC) undergoes dedifferentiation into aggressive poorly differentiated (PDTC) or anaplastic (ATC) carcinomas in 10–15% of cases, a process potentially driven by cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME), though their spatiotemporal dynamics remain poorly understood. Resveratrol (Res), a natural compound, has shown anticancer potential by promoting redifferentiation and apoptosis while inhibiting oncogenic signaling, suggesting utility in countering PTC dedifferentiation. Using spatial transcriptomics (10× Visium) on three surgical specimens, we obtained 14,191 high-quality spots annotated via UMAP and Leiden clustering into seven cell types, including CAFs, T cells, B cells, and others. Comparative gene expression and functional enrichment analyses revealed CAFs in poorly differentiated regions exhibited heightened glycolytic activity, correlated with ZFP57 upregulation and PKM2 induction. Glycolysis was validated through immunofluorescence, Seahorse assays, glucose/lactate measurements, and ZFP57-PKM2 reporter assays. CAF-conditioned media promoted PTC proliferation, invasion, and dedifferentiation while reducing radioiodine uptake in co-culture models. In xenografts, ZFP57 overexpression increased tumor growth and impaired radioiodine retention, whereas Res suppressed ZFP57, restored differentiation, enhanced radioiodine avidity, and inhibited glycolysis. Mechanistically, CAF-secretated lactate activated TGF-β/Smad2/3 signaling, fostering dedifferentiation and malignancy. Resveratrol reversed these effects by targeting ZFP57, normalizing CAF metabolism, and restoring PTC differentiation, indicating a promising therapeutic strategy against PTC progression.

Indexed as

Cancer-Associated FibroblastsCarrier ProteinsLactic AcidMembrane ProteinsResveratrolThyroid HormonesThyroid NeoplasmsAnimalsCell DedifferentiationCell Line, TumorHumansMiceThyroid Hormone-Binding ProteinsXenograft Model Antitumor AssaysCarrier ProteinsLactic AcidMembrane ProteinsResveratrolThyroid Hormone-Binding ProteinsThyroid HormonesCancer-associated fibroblastsDedifferentiationGlycolysisPapillary thyroid carcinomaSpatial transcriptomics

Identifiers

PMID41761234
PMCPMC13049851

What OpenQuestion 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 OpenQuestion graph.