ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Chemotherapy-Activated GSK3β-DNMT1 Signaling Upregulates CD47 to Evade Macrophage Phagocytosis and Drive Temozolomide Resistance in Glioblastoma.
Jie Li, Shuai Ying, Yi Zhang, Jingjing Wang, Quan Wan, Lingli Gong, Daxing Xu, Zhenkun Yang, Hongnian Lu, Ying Yin and 2 more
Abstract read
In one paragraphArticle in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
12 authors.
Jie Li *Department of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0000-0003-1365-6132 Shuai Ying *Department of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0009-0004-0125-6670 Yi Zhang *Department of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0000-0003-1139-8109 Jingjing WangDepartment of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0009-0006-7434-3200 Quan WanNeuroscience Center, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
Lingli GongDepartment of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0000-0001-5863-0476 Daxing XuDepartment of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.
Zhenkun YangDepartment of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0000-0001-5763-7748 Hongnian LuDepartment of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0009-0000-5744-6706 Ying YinDepartment of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0000-0002-8367-1103 Xiangming FangDepartment of Radiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0000-0002-8818-5382 Zhening PuDepartment of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, Jiangsu, China.ORCID https://orcid.org/0000-0003-1268-4772 Funding
Jiangsu Association for Science and Technology support project for young scientific and technological talents TJ-2023-081National Natural Science Foundation of China 82302939Phase II Special Fund for Scientific Research on Roentgen Imaging, Jiangsu Provincial Medical Association SYH-3201150-0086 [2023033]Program of Wuxi Medical Center, Nanjing Medical University WMCC202402Program of Wuxi Medical Center, Nanjing Medical University WMCG202517Program of Wuxi Medical Center, Nanjing Medical University WMCJ202403The "333" Engineering Project Jiangsu Province (2024) 3-2416The medical Expert Team Program of Wuxi Taihu Talent Plan THRC-TD-YXYXK-2021The Scientific and Technological Tackling (Basic Research) of TaihuLight K20231054The Scientific and Technological Tackling (Basic Research) of TaihuLight K20241018The Talents of Double Hundred Talent Plan BJ2023024The Talents of Double Hundred Talent Plan HB2023017Wuxi Health Commission Youth Program Q202217Wuxi Health Commission Youth Program Q202322Wuxi Medical Innovation Team CXTD2021006
6 · The paper itselfAbstract
Temozolomide (TMZ) remains the first-line therapy for glioblastoma (GBM) patients. However, the mechanisms underlying the emergence of acquired TMZ resistance after treatment are unclear. Here, we reveal the critical role of macrophage phagocytosis in GBM recurrence and acquired TMZ resistance. Mechanistically, TMZ treatment sustained GSK3β activation and promoted its interaction with DNMT1. This led to the phosphorylation of DNMT1 at the previously unrecognized S977 site for its K981-dependent ubiquitination and destabilization. The downregulation of DNMT1 leads to hypomethylation of the CD47 promoter and increases the expression of CD47, a key inhibitor of macrophage phagocytosis. Elevated CD47 expression suppresses macrophage phagocytosis and promotes the survival of TMZ-treated GBM cells. The small molecule WIN 51708 disrupts the p-GSK3β-Y216-DNMT1 interaction, which stabilizes DNMT1, decreases CD47 expression, restores phagocytosis in vivo, and resensitizes tumors to TMZ. The GSK3β-DNMT1-CD47 axis was found to be conserved in a TMZ-resistant PDX model and in samples from patients with recurrent GBM, supporting its clinical translational value. Our findings underscore the potential of the combined administration of WIN 51708 and TMZ as a strategy to resensitize GBM tumors.
Indexed as
CD47chemoresistanceDNA methylationglioblastomatumor‐associated macrophages
Identifiers
PMID42667153
PMCPMC13525619
What Socratic holds
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