CD47 blockade enhances cisplatin sensitivity by inhibiting DNA repair gene expressionOA
CD47,a cell surface transmembrane glycoprotein,is an innate immune checkpoint that suppresses phagocytic clearance.Emerging evidence suggests that CD47 has noncanonical functions.However,its involvement in chemotherapy resistance is not well understood.Our study reveals that cisplatin treatment upregulates CD47 expression across multiple cancer cell lines.Cisplatin induces the expression of CD47 through the ATM/NF‑κB signaling pathway.Genetic ablation of CD47 dramatically sensitizes cancer cells to cisplatin.Mechanistically,CD47 depletion potentiates cisplatin‑induced DNA damage,as demonstrated by elevatedγH2AX formation and ATM phosphorylation.Knockdown of CD47 inhibits the expression of DNA repair genes ERCC1,FANCA,and BRCA2 through the ATM/NF‑κB pathway.Remarkably,CD47 blockade with neutralizing antibodies recapitulates these effects,synergistically potentiating cisplatin’s DNA‑damaging capacity while suppressing DNA repair capacity.CD47 blockade also potentiates cisplatin’s tumor inhibitory effect in vivo.These findings establish a novel mechanism whereby CD47 promotes cisplatin resistance through transcriptional regulation of DNA repair pathway,providing rationale for combining CD47‑targeted therapies with conventional chemotherapy.This dual approach could simultaneously overcome immune evasion while enhancing treatment efficacy.
Xingqian Liu;Jie Lun;Jianxin Xu;Liyuan Jing;Yuying Zhang;Yu Wang;Zhengyu Jin;Mengchao Yu;Jing Fang
Cancer Institute of the Affiliated Hospital of Qingdao University,Qingdao 266071,China School of Basic Medicine,Qingdao University,Qingdao 266071,ChinaCancer Institute of the Affiliated Hospital of Qingdao University,Qingdao 266071,ChinaCancer Institute of the Affiliated Hospital of Qingdao University,Qingdao 266071,ChinaCancer Institute of the Affiliated Hospital of Qingdao University,Qingdao 266071,China School of Basic Medicine,Qingdao University,Qingdao 266071,ChinaSchool of Public Health,Qingdao University,Qingdao 266071,ChinaCancer Institute of the Affiliated Hospital of Qingdao University,Qingdao 266071,ChinaCancer Institute of the Affiliated Hospital of Qingdao University,Qingdao 266071,China School of Basic Medicine,Qingdao University,Qingdao 266071,ChinaCentral Laboratory,Qingdao Municipal Hospital,Qingdao 266071,ChinaCancer Institute of the Affiliated Hospital of Qingdao University,Qingdao 266071,China School of Basic Medicine,Qingdao University,Qingdao 266071,China
医药卫生
CD47cancerchemotherapy resistanceDNA repair genecisplatin
《Acta Biochimica et Biophysica Sinica》 2026 (5)
P.1132-1143,12
supported by the grants from the National Natural Science Foundation of China(No.82073061)Shandong Provincial Natural Science Foundation(No.ZR2024MC144)Ministry of Science and Technology of China(No.2020YFA0803301).
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