Evidence map›Paper›PMID 42476970›Full record

ArticleCell death & disease2026

LSD1-GLS2 axis drives subtype-specific chemoresistance in pancreatic cancer through glutaminolysis reprogramming.

Zhefang Wang, Qiu Huang, Jiangang Zhao, Zicheng Lyu, Feng Ju, Bo You, Jie Wang, Qiongzhu Dong, Margarete Odenthal, Alexander Quaas and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Zhefang WangDepartment of General, Visceral, Thoracic and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0002-2297-2586
Qiu HuangDepartment of General, Visceral, Thoracic and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany.
Jiangang ZhaoDepartment of General, Visceral, Thoracic and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany.
Zicheng LyuDepartment of General, Visceral, Thoracic and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany.
Feng JuDepartment of General, Visceral, Thoracic and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany.
Bo YouInstitute of Otolaryngology head and neck surgery, Affiliated Hospital of Nantong University, Nantong, PR China.ORCID http://orcid.org/0000-0002-3602-5264
Jie WangInstitute of Pathology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.ORCID http://orcid.org/0009-0002-9350-8817
Qiongzhu DongKey Laboratory of Whole-period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, Shanghai, PR China.ORCID http://orcid.org/0000-0002-2433-7199
Margarete OdenthalInstitute of Pathology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
Alexander QuaasInstitute of Pathology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
Kalliope N DiakopoulosComprehensive Cancer Center München, Institute for Tumor Metabolism, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Bavaria, Germany.
Hana AlgülComprehensive Cancer Center München, Institute for Tumor Metabolism, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Bavaria, Germany.
Maximilian ReichertDepartment of Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-8611-5639
Christiane J BrunsDepartment of General, Visceral, Thoracic and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany. christiane.bruns@uk-koeln.de.ORCID http://orcid.org/0000-0001-6590-8181
Yue ZhaoDepartment of General, Visceral, Thoracic and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany. yue.zhao@uk-koeln.de.ORCID http://orcid.org/0000-0002-6790-3402

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) SATURN301KD2206LNational Science Foundation of China | Young Scientists Fund 82102701Universität zu Köln (University of Cologne) 86/2024
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy due to its aggressive biology and therapeutic resistance. Lysine-specific demethylase 1 (LSD1), an epigenetic regulator, is overexpressed in PDAC and linked to poor prognosis, yet its context-dependent roles in metabolic subtypes and chemoresistance remain undefined. Here, we show that LSD1 knockdown has opposing, subtype-specific effects on chemotherapeutic responses: it sensitized RSK-subtype cells (L3.6pl, PANC-1) to chemotherapy but induced resistance in KRAS-subtype cells (BxPC-3, TBO368). Integrated analyses revealed mitochondrial dysfunction and defective mitophagy as hallmarks distinguishing KRAS- from RSK-subtype PDAC. Critically, mitochondrial targeting through respiratory modulation or mitophagy manipulation overrides LSD1-mediated subtype-specific chemoresistance, establishing mitochondrial fitness as the mechanistic determinant. Mechanistically, LSD1 transcriptionally regulates GLS2 to drive glutamine metabolic reprogramming, promoting reductive carboxylation in KRAS-subtype cells and oxidative metabolism in RSK-subtype cells. Our work establishes the LSD1-GLS2 axis as a metabolic switch controlling PDAC chemosensitivity and provides a framework for subtype-specific therapeutic strategies.

Indexed as

Carcinoma, Pancreatic DuctalDrug Resistance, NeoplasmGlutamineHistone DemethylasesPancreatic NeoplasmsAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingMitochondriaMitophagyGlutamineHistone DemethylasesKDM1A protein, human

Identifiers

PMID42476970
PMCPMC13385623

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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.