{"title":"USP33 is an integrin α6 deubiquitinase and promotes esophageal squamous cell carcinoma cell migration and metastasis.","authors":"Qinglei Hang, Shiying Zuo, Yawen Yang, Yuanzhi Wang, Caimin Li, Wenqian Li, Jingya Guo, Sicong Hou, Haifeng Huang","doi":"10.1007/s00432-024-06041-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The deubiquitinating enzymes (DUBs) have been linked to cancer initiation and progression. Although ubiquitin-specific protease 33 (USP33) represents a significant factor in regulating various tumor cell behaviors, its specific biological functions and precise mechanisms in esophageal squamous cell carcinoma (ESCC) progression remain unclear.</p><p><strong>Methods: </strong>The expressions of USP33 mRNA in GEO databases, clinical ESCC samples, and USP33 protein were analyzed using bioinformatics, RT-PCR, and immunohistochemistry, respectively. Using Kaplan-Meier survival curves, the log-rank test was used to determine the cumulative survival rate. Western blotting was used to determine indicated protein expression. The cell biological functions were evaluated by cell growth assay, transwell, cell adhesion, and cell spreading assay, respectively. The interaction between USP33 and integrins was detected by immunoprecipitation, and the deubiquitination was performed by deubiquitination assay. The metastatic ability was checked by tail vein injection.</p><p><strong>Results: </strong>A significant positive correlation was found between USP33 expression and clinical TNM stage, T classification, and poor prognosis in patients with ESCC. USP33 promoted laminin-dependent adhesion, spreading, and migration of ESCC cells but not their proliferation. Mechanistically, USP33 mediates cell migration through binding, deubiquinating, and stabilizing integrin α6. USP33 knockdown could inhibit ESCC cell migration and metastasis majorly through integrin α6.</p><p><strong>Conclusion: </strong>This study reveals a novel mechanism of USP33 in promoting laminin-dependent ESCC cell migration and metastasis through integrin α6, suggesting that USP33 may be a promising target for treating ESCC.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"150 12","pages":"511"},"PeriodicalIF":2.7000,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cancer Research and Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00432-024-06041-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: The deubiquitinating enzymes (DUBs) have been linked to cancer initiation and progression. Although ubiquitin-specific protease 33 (USP33) represents a significant factor in regulating various tumor cell behaviors, its specific biological functions and precise mechanisms in esophageal squamous cell carcinoma (ESCC) progression remain unclear.
Methods: The expressions of USP33 mRNA in GEO databases, clinical ESCC samples, and USP33 protein were analyzed using bioinformatics, RT-PCR, and immunohistochemistry, respectively. Using Kaplan-Meier survival curves, the log-rank test was used to determine the cumulative survival rate. Western blotting was used to determine indicated protein expression. The cell biological functions were evaluated by cell growth assay, transwell, cell adhesion, and cell spreading assay, respectively. The interaction between USP33 and integrins was detected by immunoprecipitation, and the deubiquitination was performed by deubiquitination assay. The metastatic ability was checked by tail vein injection.
Results: A significant positive correlation was found between USP33 expression and clinical TNM stage, T classification, and poor prognosis in patients with ESCC. USP33 promoted laminin-dependent adhesion, spreading, and migration of ESCC cells but not their proliferation. Mechanistically, USP33 mediates cell migration through binding, deubiquinating, and stabilizing integrin α6. USP33 knockdown could inhibit ESCC cell migration and metastasis majorly through integrin α6.
Conclusion: This study reveals a novel mechanism of USP33 in promoting laminin-dependent ESCC cell migration and metastasis through integrin α6, suggesting that USP33 may be a promising target for treating ESCC.
期刊介绍：
The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses.
The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
