DMAP1 Deficiency Suppresses Lung Cancer Progression by Destabilizing Replication Fork and Activating IFN Signaling‐Mediated Anti‐tumor Immunity
Year: 2026
Type: article
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.
Source: Advanced Science
Authors: Kan Huang, Xi Dai, Shuaihu Li, Yingxue Chen, Yaxin Yu, Lin Wang, Kun Liu, Shuhan Lyu, Chongyang Li, Yihua Sun, Fei Li
Institutions: Shanghai Medical College of Fudan University, Fudan University, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Pudong Medical Center, University of Southern California, Tongji University, Shanghai Pulmonary Hospital, Shanghai Jiao Tong University, Shanghai Chest Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,730
OpenAlex ID: W7142730553