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World J Stem Cells. Sep 26, 2026; 18(9): 124540
Published online Sep 26, 2026. doi: 10.4252/wjsc.124540
Published online Sep 26, 2026. doi: 10.4252/wjsc.124540
MED12 mutation activates Notch signaling to enhance cancer stemness and suppress CD8+ T cell cytotoxicity in lung cancer
Ying Yang, Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital of Fudan University, Shanghai 201508, China
Jin-Long Zhong, Jia-Yuan Liu, Department of Thoracic Surgery, Jinshan Hospital of Fudan University, Shanghai 201508, China
Author contributions: Yang Y and Zhong JL contributed to writing - original draft; Yang Y contributed to conceptualization, investigation, resources, and supervision; Zhong JL contributed to data curation, project administration, validation, and visualization; Liu JY contributed to formal analysis, methodology, software, funding acquisition, and writing - review and editing.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Supported by 2024 Jinshan District Health Special Research Project - General Program, No. JSKJ-KTMS-2024-02.
Institutional review board statement: There are no experiments involving human participants or animal subjects were required.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Corresponding author: Jia-Yuan Liu, Chief Physician, Department of Thoracic Surgery, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai 201508, China. ljyuan1985@163.com
Received: June 22, 2026
Revised: July 18, 2026
Accepted: September 18, 2026
Published online: September 26, 2026
Processing time: 96 Days and 17.7 Hours
Revised: July 18, 2026
Accepted: September 18, 2026
Published online: September 26, 2026
Processing time: 96 Days and 17.7 Hours
Core Tip
Core Tip: Mediator complex subunit 12 mutation in lung cancer cells activates Notch signaling, which concurrently promotes cancer stemness - characterized by enhanced sphere formation and increased ALDH1+ cells - and induces immune evasion via upregulation of surface programmed death ligand-1 on tumor cells. This leads to impaired CD8+ T cell chemotaxis, reduced release of effector molecules (interferon-γ, tumor necrosis factor-α, perforin, granzyme-B), and increased programmed cell death 1 expression. Notch inhibitor DAPT reverses these pro-tumor effects.