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Identification of RAPGEF3 as the therapeutic vulnerability of basal-subtype lung squamous cell carcinoma

文献类型：期刊论文

作者Zhou, Yijia3,4; Wang, Hua4; Tang, Shijie4; He, Yayi5; Yang, Cai-guang6,7; Chen, Luonan2,4; Ji, Hongbin1,2,3,4
刊名ONCOGENE
出版日期2025-09-08
卷号44期号:34页码:3142-3148
ISSN号0950-9232
DOI10.1038/s41388-025-03532-8
英文摘要Lung squamous cell carcinoma (LUSC), particularly the basal-subtype, remains a leading cause of cancer-related mortality, with limited therapeutic options and poor survival rates. In this study, we identify RAPGEF3 as a critical driver of malignant progression in basal-subtype LUSC. Our findings show that RAPGEF3 is significantly upregulated in basal-subtype LUSC and plays a pivotal role in tumor progression by activating the RAP1A-AKT signaling axis, essential for cell proliferation and survival. We demonstrate that inhibiting RAPGEF3 with the selective inhibitor ESI-09 significantly suppresses tumor growth in patient-derived xenograft (PDX) models without notable toxicity. Furthermore, our results reveal that RAP1A, rather than its paralog RAP1B, mediates tumor survival and proliferation through AKT signaling, providing new insights into the functional differences between these isoforms. Given the lack of targeted therapies for basal-subtype LUSC, RAPGEF3 emerges as a novel and promising therapeutic target. These findings not only contribute to understanding the molecular mechanisms of basal-subtype LUSC but also suggest that RAPGEF3-targeted therapies may be applicable to other cancers with similar oncogenic signaling pathways.
资助项目This work was supported by the National Key Research and Development Program of China (2022YFA1103900 to H.J. ; 2020YFA0803300 to H.J.) ; the National Natural Science Foundation of China (82341002 to H.J., 32293192 to H.J., 82030083 to H.J., 82473426 to L.H.[2022YFA1103900] ; This work was supported by the National Key Research and Development Program of China (2022YFA1103900 to H.J. ; 2020YFA0803300 to H.J.) ; the National Natural Science Foundation of China (82341002 to H.J., 32293192 to H.J., 82030083 to H.J., 82473426 to L.H.[2020YFA0803300] ; National Key Research and Development Program of China[82341002] ; National Key Research and Development Program of China[32293192] ; National Key Research and Development Program of China[82030083] ; National Key Research and Development Program of China[82473426] ; National Key Research and Development Program of China[82173340] ; National Key Research and Development Program of China[82273400] ; National Key Research and Development Program of China[82203306] ; National Key Research and Development Program of China[82372763] ; National Key Research and Development Program of China[82303916] ; National Key Research and Development Program of China[82303039] ; National Key Research and Development Program of China[T2341007] ; National Key Research and Development Program of China[12131020] ; National Key Research and Development Program of China[31930022] ; National Key Research and Development Program of China[T2350003] ; National Key Research and Development Program of China[82303575] ; National Natural Science Foundation of China[SSMU-ZLCX20180500] ; Innovative research team of high-level local universities in Shanghai
WOS研究方向Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
语种英语
WOS记录号WOS:001547704100001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/321291]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Ji, Hongbin
作者单位1.Westlake Univ, Sch Med, Hangzhou, Peoples R China
2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Hangzhou, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, Key Lab Multicell Syst, Shanghai, Peoples R China
5.Tongji Univ, Med Sch, Shanghai Pulm Hosp, Dept Med Oncol,Sch Med,Canc Inst, Shanghai, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
7.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Zhou, Yijia,Wang, Hua,Tang, Shijie,et al. Identification of RAPGEF3 as the therapeutic vulnerability of basal-subtype lung squamous cell carcinoma[J]. ONCOGENE,2025,44(34):3142-3148.
APA Zhou, Yijia.,Wang, Hua.,Tang, Shijie.,He, Yayi.,Yang, Cai-guang.,...&Ji, Hongbin.(2025).Identification of RAPGEF3 as the therapeutic vulnerability of basal-subtype lung squamous cell carcinoma.ONCOGENE,44(34),3142-3148.
MLA Zhou, Yijia,et al."Identification of RAPGEF3 as the therapeutic vulnerability of basal-subtype lung squamous cell carcinoma".ONCOGENE 44.34(2025):3142-3148.

入库方式： OAI收割

来源：上海药物研究所

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