Evidence map›Paper›PMID 40281343›Full record

ArticleNature chemical biology2025

PSAT1 impairs ferroptosis and reduces immunotherapy efficacy via GPX4 hydroxylation.

Peixiang Zheng, Zhiqiang Hu, Yuli Shen, Lina Gu, Yuan Ouyang, Yuran Duan, Guimei Ji, Bofei Dong, Yanni Lin, Ting Wen and 26 more

Abstract read
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In one paragraph

Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

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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

36 authors.

Peixiang Zheng *Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Zhiqiang Hu *Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.ORCID http://orcid.org/0000-0003-1313-3470
Yuli Shen *Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Lina Gu *Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Yuan OuyangLaboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuran DuanZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Guimei JiZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Bofei DongZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Yanni LinZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Ting WenZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Qi TianZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Yueru HouZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.ORCID http://orcid.org/0009-0000-3573-7473
Qimin ZhouDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xue SunDepartment of Surgical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Xiaohan ChenDepartment of Surgical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Katherine L WangSt. Agnes Academy, Houston, TX, USA.
Shudi LuoZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Shiqi WuZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Yuening SunDepartment of Pharmacy, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Min LiZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Liwei XiaoZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Qingang WuZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Ying MengZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.ORCID http://orcid.org/0000-0002-1165-9009
Guijun LiuZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Zheng WangZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Xueli BaiDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0002-2934-0880
Shengzhong DuanStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China.ORCID http://orcid.org/0000-0002-4866-3167
Yuan DingDepartment of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yanli BiKey Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.
Yuhao WangZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Gaopeng LiDepartment of Colorectal Surgery and Oncology of the Second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Xiaoguang LiuCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education) of the Second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.ORCID http://orcid.org/0000-0001-6977-5128
Zhimin LuZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Xiaohong WuNHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Harbin Medical University, Harbin, China. wuxiaohong@hrbmu.edu.cn.ORCID http://orcid.org/0000-0002-8259-3027
Zhiyuan TangDepartment of Pharmacy, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China. tzy@ntu.edu.cn.ORCID http://orcid.org/0000-0002-3786-7690
Daqian XuZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China. xudaqian@zju.edu.cn.ORCID http://orcid.org/0000-0003-0478-2997

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor cells adapt to the inflammatory tumor microenvironment (TME) and develop resistance to immunotherapy, with ferroptosis being a major form of tumor cell death. However, the mechanisms by which tumor cells coordinate TME stimuli and their unique metabolic traits to evade ferroptosis and develop resistance to immunotherapy remain unclear. Here we showed that interferon-γ (IFNγ)-activated calcium/calmodulin-dependent protein kinase II phosphorylates phosphoserine aminotransferase 1 (PSAT1) at serine 337 (S337), allowing it to interact with glutathione peroxidase 4 (GPX4) and stabilize the protein, counteracting ferroptosis. PSAT1 elevates GPX4 stability by promoting α-ketoglutarate-dependent PHD3-mediated GPX4 proline 159 (P159) hydroxylation, disrupting its binding to HSC70 and inhibiting autophagy-mediated degradation. In mice, reconstitution of PSAT1 S337A or GPX4 P159A promotes ferroptosis and suppresses triple-negative breast cancer (TNBC) progression. Blocking PSAT1 pS337 with CPP elevates IFNγ-induced ferroptosis and enhances the efficacy of programmed cell death protein 1 (PD-1) antibodies in TNBC. Additionally, PSAT1-mediated GPX4 hydroxylation correlates with poor immunotherapy outcomes in patients with TNBC, highlighting PSAT1's noncanonical role in suppressing ferroptosis and immunotherapy sensitivity.

Indexed as

FerroptosisImmunotherapyPhospholipid Hydroperoxide Glutathione PeroxidaseTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFemaleHumansHydroxylationInterferon-gammaMiceTumor MicroenvironmentInterferon-gammaPhospholipid Hydroperoxide Glutathione Peroxidase

Identifiers

PMID40281343

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Registered trials

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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.