Evidence map›Paper›PMID 41857421›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2026

Tyrosine hydroxylase as a therapeutic target: insights from adrenergic nerve and TNBC cell interactions.

Yichen Luo, Yanhong Han, Huilong Nie, Minghao Feng, Cuiting Wei, Xiuling Ma, Kefeng Li, Zhuangzhuang Zhang, Guangxue Wang, Wenjun Pan and 7 more

Abstract read
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In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

17 authors.

Yichen Luo *Department of Pathology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
Yanhong Han *Center for Biological Science and Technology, Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, Department of Biology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, 519087, Guangdong, China.
Huilong Nie *Department of Obstetrics and Gynecology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
Minghao Feng *Department of Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Cuiting WeiDepartment of Obstetrics and Gynecology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
Xiuling MaFaculty of Applied Sciences, Macao Polytechnic University, Macau SAR, 999078, China.
Kefeng LiFaculty of Applied Sciences, Macao Polytechnic University, Macau SAR, 999078, China.
Zhuangzhuang ZhangGuangdong Provincial Engineering Research Center of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
Guangxue WangResearch Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Wenjun PanGuangdong Provincial Engineering Research Center of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
Xueyang LiGuangdong Provincial Engineering Research Center of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
Liutong YiDepartment of Pathology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
De-Yun WangDepartment of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, 119228, Singapore.
Xian-Tao ZengCenter for Evidence‑Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Yongkang QiaoCenter for Biological Science and Technology, Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, Department of Biology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, 519087, Guangdong, China. ykqiao@bnu.edu.cn.ORCID http://orcid.org/0000-0002-1052-6722
Yan YanGuangdong Provincial Engineering Research Center of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China. yanyan35@mail.sysu.edu.cn.
Yujing LinDepartment of Pathology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China. linyj@mail.sysu.edu.cn.

Funding

National Natural Science Foundation of China 8200262
6 · The paper itself

Abstract

The sympathetic adrenergic nerves (SAN) play a significant role in the malignant transformation of breast cancer cells through the activity of norepinephrine (NE). However, the role of tyrosine hydroxylase (TH), a key enzyme of the NE synthesis, in the interaction between the SAN and triple-negative breast cancer (TNBC) cells has not been sufficiently explored, and whether TH can be a therapeutic target for TNBC has not been reported. TH expression in TNBC was examined by analyzing data from an online database and immunohistochemical analysis of our clinical samples. Cell proliferation and drug sensitivity were assessed upon coculture with fluorescently labeled cells using IncuCyte. Changes in the expression of DNA damage and apoptosis-associated proteins were assessed by western blotting. TH expression and NE synthesis in PC12 cells after their coculture with TNBC cells were measured by RT-qPCR, immunofluorescence, and ELISA. RNA sequencing was conducted on the cells before and after coculture. TH expression was relatively high in TNBC tumor tissues and closely associated with prognosis. SAN promoted TNBC cell proliferation through NE and reduced TNBC cell sensitivity to chemotherapeutic agents. Additionally, tumor cells induced TH expression in PC12 cells through nerve growth factor (NGF) secretion. Knocking down TH and using TH inhibitors effectively reversed the proliferation-promoting and drug sensitivity-reducing effects of SAN in TNBC cells. TH may be a central molecule in the positive feedback loop between TNBC cells and SAN. TH is a potential prognostic biomarker and can also serve as a therapeutic target for TNBC. KEY MESSAGES: The overexpression of the sympathetic nerve biomarker tyrosine hydroxylase (TH) in triple-negative breast cancer (TNBC) is an indicator for clinical staging, prognosis, and targeted therapy. There is a feedback loop where TH in nerves produces NE, worsening TNBC and reducing chemotherapy effectiveness. TNBC cell then increases TH expression, further boosting NE production. Furthermore, blocking the activity of TH could effectively inhibit this phenotype.

Indexed as

Adrenergic NeuronsCell CommunicationTriple Negative Breast NeoplasmsTyrosine 3-MonooxygenaseAnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCoculture TechniquesFemaleGene Expression Regulation, NeoplasticHumansNorepinephrinePC12 CellsRatsAntineoplastic AgentsNorepinephrineTyrosine 3-Monooxygenase3D mammosphereChemotherapy sensitivityNeural-tumor coculture modelNorepinephrineTriple-negative breast cancer (TNBC)Tyrosine hydroxylase

Identifiers

PMID41857421

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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.