Evidence map›Paper›PMID 42265770›Full record

ArticleJournal of experimental & clinical cancer research : CR2026

Loss of CSE couples with BRAF V600E to fuel thyroid cancer metastatic progression through zinc-dependent activation of the EMT machinery.

Shichen Xu, Huixin Yu, Hongxun Wu, Zongfu Pan, Jiajie Xu, Yun Zhu, Botao Huang, Gangming Cai, Xiaobo Gu, Min Yang and 6 more

Abstract read
PubMed 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. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Shichen XuNational Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qian Rong Road, Wuxi, 214063, China.
Huixin YuNational Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qian Rong Road, Wuxi, 214063, China.
Hongxun WuJiangsu Institute of Nuclear Medicine Jiangyuan Hospital of Jiangsu Province, Wuxi, 214063, China.
Zongfu PanDepartment of Pharmacy, Center for Clinical Pharmacy, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310014, China.
Jiajie XuDepartment of Head and Neck Surgery, Otolaryngology & Head and Neck Center, Cancer Center, Zhejiang Provincial People's Hospital, Hangzhou, China.
Yun ZhuJiangsu Institute of Nuclear Medicine Jiangyuan Hospital of Jiangsu Province, Wuxi, 214063, China.
Botao HuangJiangsu Institute of Nuclear Medicine Jiangyuan Hospital of Jiangsu Province, Wuxi, 214063, China.
Gangming CaiJiangsu Institute of Nuclear Medicine Jiangyuan Hospital of Jiangsu Province, Wuxi, 214063, China.
Xiaobo GuJiangsu Institute of Nuclear Medicine Jiangyuan Hospital of Jiangsu Province, Wuxi, 214063, China.
Min YangNational Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qian Rong Road, Wuxi, 214063, China.
Donghui PanNational Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qian Rong Road, Wuxi, 214063, China.
Jie PanSchool of Life Sciences, Nanjing Medical University, Changzhou, China.
Jing WuNational Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qian Rong Road, Wuxi, 214063, China.
Xian ChengNational Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qian Rong Road, Wuxi, 214063, China.
Jiandong BaoJiangsu Institute of Nuclear Medicine Jiangyuan Hospital of Jiangsu Province, Wuxi, 214063, China.
Li ZhangNational Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qian Rong Road, Wuxi, 214063, China. zhangli@jsinm.org.ORCID http://orcid.org/0000-0002-1740-8833

Funding

National Natural Science Foundation of China 81972503National Natural Science Foundation of China 82103656Science and Research Foundation of Jiangsu Commission of Health M2024084Science and Research Foundation of Wuxi Science & Technology Bureau K20231034Science and Research Foundation of Wuxi Science & Technology Bureau Y20242123
6 · The paper itself

Abstract

backgroundBRAF V600E, the principal oncogenic driver in papillary thyroid carcinoma (PTC), strongly correlated with lymph node metastasis, yet the underlying molecular mechanisms remain elusive.

methodsThis study screened effector related to the BRAF V600E mutation and PTC progression through bioinformatics analysis. The precise functional roles and regulatory networks of cystathionine γ-lyase (CSE), a primary hydrogen sulfide (H₂S)-producing enzyme, in thyroid cancer metastasis were then investigated in cell and mice models. Finally, these findings were further validated in a cohort of clinical pathological samples.

resultsWe identified that CSE is aberrantly silenced in advanced thyroid cancer. Mechanistically, BRAF V600E-driven MAPK activation upregulates miR-31-5p, which directly targets the CSE 3'UTR to inhibit its translation. The consequent H₂S deficiency disrupts intracellular metallo-homeostasis, triggering intracellular zinc accumulation that stabilizes Zeb1, MMP-2, thereby orchestrating the epithelial-mesenchymal transition (EMT). Critically, the metastatic potential of thyroid cancer cells relies strictly on CSE enzymatic activity. Pharmacological reconstitution of the H₂S pool using exogenous donors effectively bypasses CSE enzymatic deficiency, eliminates excess zinc, and reactivates metastasis-suppressive signaling.

conclusionsThese findings uncover a novel miR-31-5p/CSE/H₂S/Zinc axis that fuels BRAF-driven progression. These findings provide a compelling mechanistic rationale for utilizing H₂S-based interventions as a potential therapeutic strategy against BRAF-driven thyroid cancer metastasis.

Indexed as

Cystathionine gamma-LyaseEpithelial-Mesenchymal TransitionProto-Oncogene Proteins B-rafThyroid NeoplasmsAnimalsCell Line, TumorDisease ProgressionGene Expression Regulation, NeoplasticHumansHydrogen SulfideMiceMicroRNAsMutationNeoplasm MetastasisBRAF protein, humanCystathionine gamma-LyaseHydrogen SulfideMicroRNAsProto-Oncogene Proteins B-rafBRAF V600Ecystathionine γ-lyasehydrogen sulfideMetastasisPapillary thyroid carcinomaZinc homeostasis

Identifiers

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.