{"title":"Vacuole Protein Sorting 18 (Vps18) Suppresses Epithelial Growth Factor Receptor (EGFR) Expression and Tumorigenesis.","authors":"Wuhou Dai, Shujing Zhang, Shunfei Yan, Hao Zhang, Sha Zou, Tonglu Yu, Wufan Tao, Hengning Ke, Xingrong Du","doi":"10.1016/j.jbc.2025.110447","DOIUrl":null,"url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related deaths worldwide. While lysosomal degradative function is critical for cellular homeostasis, its role in lung cancer pathogenesis remains poorly understood. Here we identify Vps18 as an important tumor suppressor in murine lung tumorigenesis. Genetic ablation of Vps18 accelerates lung tumorigenesis in LSL-K-Ras mice, accompanied by enhanced tumor cell proliferation. Mechanistically, Vps18 deficiency elevates EGFR protein level and activates the ERK-MAPK signaling pathway in lung tumors. Strikingly, expression of dominant-negative EGFR (dnEGFR) partially suppresses the tumor-promoting effects of Vps18 loss. Our findings unveil a novel Vps18-EGFR-ERK axis in lung cancer and may inform the development of targeted therapeutic strategies.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110447"},"PeriodicalIF":4.0000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biological Chemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jbc.2025.110447","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Lung cancer remains the leading cause of cancer-related deaths worldwide. While lysosomal degradative function is critical for cellular homeostasis, its role in lung cancer pathogenesis remains poorly understood. Here we identify Vps18 as an important tumor suppressor in murine lung tumorigenesis. Genetic ablation of Vps18 accelerates lung tumorigenesis in LSL-K-Ras mice, accompanied by enhanced tumor cell proliferation. Mechanistically, Vps18 deficiency elevates EGFR protein level and activates the ERK-MAPK signaling pathway in lung tumors. Strikingly, expression of dominant-negative EGFR (dnEGFR) partially suppresses the tumor-promoting effects of Vps18 loss. Our findings unveil a novel Vps18-EGFR-ERK axis in lung cancer and may inform the development of targeted therapeutic strategies.
期刊介绍：
The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.
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