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journal article·2026-06Open access

DMAP1 Deficiency Suppresses Lung Cancer Progression by Destabilizing Replication Fork and Activating IFN Signaling‐Mediated Anti‐tumor Immunity

Kan Huang, Xi Dai, Shuaihu Li, Yingxue Chen, Yaxin Yu, Lin Wang, Kun Liu, Shuhan Lyu, Chongyang Li, Yihua Sun, Fei Li

Advanced Science· Volume 13· Issue 33
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Source abstract

Abstract

ABSTRACT Despite substantial progress in targeted and immune therapies, lung cancer remains the leading cause of cancer‐related mortality, highlighting the urgent need for novel therapeutic strategies. Through a CRISPR‐based knock‐out screen, we identified the DNA methyltransferase 1‐associated protein 1 (DMAP1) as a critical regulator of lung cancer progression. Functional studies demonstrated that DMAP1 deficiency exerts its anti‐tumor effects through attenuating tumor cell proliferation and activating T cell‐mediated adaptive anti‐tumor effects. Mechanistically, DMAP1 deficiency causes replication fork retardance, disturbs genome stability, and induces endogenous DNA damage, thereby activating IFN signaling‐mediated anti‐tumor immune response. Clinical data analyses revealed that high DMAP1 expression is associated with a “cold” tumor microenvironment and poorer overall survival in lung cancer. These findings significantly advance our knowledge of DMAP1's function in lung cancer development and offer a scientific basis for designing novel treatment approaches.
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Research context

OpenAlex topics: interferon and immune responses · Epigenetics and DNA Methylation · Ferroptosis and cancer prognosis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of pathology, School of Basic Medical Sciences Department of Thoracic Surgery, Fudan University Shanghai Cancer Center Fudan University Shanghai China

Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai China

Institute of Thoracic Oncology Fudan University Shanghai China

Department of Oncology Shanghai Medical College Fudan University Shanghai China

Department of Pathology and Frontier Innovation Center School of Basic Medicine Sciences, Shanghai Pudong Hospital Fudan University Shanghai China

Department of Medicine Keck School of Medicine University of Southern California Los Angeles USA

Department of Medical Oncology Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai China

Department of Thoracic Surgery Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

Shanghai Institute of Thoracic Oncology Shanghai China

Funding

National Natural Science Foundation of China · China Postdoctoral Science Foundation · Science and Technology Commission of Shanghai Municipality · Shanghai Municipal Health Commission · Ministry of Science and Technology of the People's Republic of China

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