A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer
文献类型：期刊论文
| 作者 | Xia, Lu7; Wang, Jichuan6; Xue, Hui5; Li, Haimeng7; Li, Qinghua7; Qin, Sen7; Yu, Chunyu4; Liu, Yanhua3,7; Gao, Yu2; Li, Lingyun1 |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2025-07-01 |
| 卷号 | 12期号:27页码:17 |
| 关键词 | CMTM6 EGFR EGFR-TKIs resistance NSCLC nanobody |
| DOI | 10.1002/advs.202410945 |
| 通讯作者 | Han, Wenling(hanwl@bjmu.edu.cn) ; Shang, Yongfeng(yshang@hsc.pku.edu.cn) ; Geng, Yong(gengyong@simm.ac.cn) ; Sun, Luyang(luyang_sun@hsc.pku.edu.cn) |
| 英文摘要 | Aberrant EGFR signaling drives non-small cell lung cancer (NSCLC) development, and despite the success of tyrosine kinase inhibitor (TKI) therapies in treating NSCLC, TKI resistance remains a major obstacle. Here, we report that the chemokine-like transmembrane protein CMTM6 is physically associated with EGFR. CMTM6 is shown to be co-localized with EGFR in recycling endosomes that are marked by RAB11, thereby preventing EGFR from lysosome-mediated degradation in NSCLC cells. The level of CMTM6 is elevated in NSCLC, and high expression of CMTM6 is associated with enhanced colocalization of CMTM6 with EGFR and RAB11 in NSCLC tumors and correlated with a poor prognosis in NSCLC patients. A CMTM6-targeting nanobody is developed and administration of this agent leads to blocking of the CMTM6-EGFR interaction, reduction of the EGFR protein level, and inhibition of the proliferation of TKI-resistant NSCLC cells in vitro and suppression of the growth of EGFR-TKI-resistant NSCLC in both cell line-derived xenografts and patient-derived xenograft models. The study indicates that CMTM6 is a stabilizer of EGFR in endocytic trafficking and provides evidence to support targeting CMTM6 as a potential therapeutic strategy to overcome TKI resistance in NSCLC treatment. |
| WOS关键词 | PD-L1 ; ACTIVATION ; MUTATIONS ; UBIQUITYLATION ; DEGRADATION ; ENDOCYTOSIS ; TRAFFICKING ; INHIBITION ; STRATEGIES ; EFFICACY |
| 资助项目 | Ministry of Science and Technology of China ; National Natural Science Foundation of China[U24A200281] ; National Natural Science Foundation of China[32350020] ; National Natural Science Foundation of China[32370620] ; National Natural Science Foundation of China[82188102] ; National Natural Science Foundation of China[31991164] ; National Natural Science Foundation of China[82171750] ; National Natural Science Foundation of China[81971472] ; Natural Science Foundation of Beijing[Z200020] ; National Key Research and Development Program of China[SQ2023YFB3200066] ; Science and Technology Commission of Shanghai Municipality[18JC1415400] ; Beijing Physician Scientist Training Project[BJPSTP-2024-10] ; National Center for Protein Sciences at Peking University[2024YXXLHGG006] ; National Center for Protein Sciences at Peking University[BMU2024PYJH026] ; National Center for Protein Sciences at Peking University[PKU2024LCXQ027] ; [2021YFA1300603] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001508686100001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318425]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Han, Wenling; Shang, Yongfeng; Geng, Yong; Sun, Luyang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Materia Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Sichuan Univ, West China Hosp, Thorac Oncol Ward, Canc Ctr, Chengdu 610041, Peoples R China 3.Peking Univ, Sch Basic Med Sci, Dept Integrat Chinese & Western Med, State Key Lab Mol Oncol,Hlth Sci Ctr, Beijing 100191, Peoples R China 4.Hangzhou Normal Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hangzhou 311121, Peoples R China 5.Peking Univ, Ctr Human Dis Genom, Hlth Sci Ctr, Sch Basic Med Sci,Dept Immunol,NHC Key Lab Med Imm, Beijing 100191, Peoples R China 6.Peking Univ, Peoples Hosp, Musculoskeletal Tumor Ctr, Beijing Key Lab Musculoskeletal Tumors, Beijing 100044, Peoples R China 7.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol,Int Canc Inst,State Key La, Beijing 100191, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xia, Lu,Wang, Jichuan,Xue, Hui,et al. A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer[J]. ADVANCED SCIENCE,2025,12(27):17. |
| APA | Xia, Lu.,Wang, Jichuan.,Xue, Hui.,Li, Haimeng.,Li, Qinghua.,...&Sun, Luyang.(2025).A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer.ADVANCED SCIENCE,12(27),17. |
| MLA | Xia, Lu,et al."A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer".ADVANCED SCIENCE 12.27(2025):17. |
入库方式： OAI收割
来源：上海药物研究所
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