دورية أكاديمية
Degradation of helicase-like transcription factor (HLTF) by β-TrCP promotes hepatocarcinogenesis via activation of the p62/mTOR axis
| العنوان: | Degradation of helicase-like transcription factor (HLTF) by β-TrCP promotes hepatocarcinogenesis via activation of the p62/mTOR axis |
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| المؤلفون: | Tan, Ye, Wu, Di, Liu, Ze-Yu, Yu, Hong-Qiang, Zheng, Xiang-Ru, Lin, Xiao-Tong, Bie, Ping, Zhang, Lei-Da, Xie, Chuan-Ming |
| المساهمون: | Lu, Hua, Third Military Medical University |
| المصدر: | Journal of Molecular Cell Biology ; volume 15, issue 2 ; ISSN 1674-2788 1759-4685 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cell Biology, Genetics, Molecular Biology, General Medicine |
| الوصف: | Helicase-like transcription factor (HLTF) has been found to be involved in the maintenance of genome stability and tumour suppression, but whether its downregulation in cancers is associated with posttranslational regulation remains unclear. Here, we observed that HLTF was significantly downregulated in hepatocellular carcinoma (HCC) tissues and positively associated with the survival of HCC patients. Mechanistically, the decreased expression of HLTF in HCC was attributed to elevated β-TrCP-mediated ubiquitination and degradation. Knockdown of HLTF enhanced p62 transcriptional activity and mammalian target of rapamycin (mTOR) activation, leading to HCC tumourigenesis. Inhibition of mTOR effectively blocked β-TrCP overexpression- or HLTF knockdown-mediated HCC tumourigenesis and metastasis. Furthermore, in clinical tissues, decreased HLTF expression was positively correlated with elevated expression of β-TrCP, p62, or p-mTOR in HCC patients. Overall, our data not only uncover new roles of HLTF in HCC cell proliferation and metastasis, but also reveal a novel posttranslational modification of HLTF by β-TrCP, indicating that the β-TrCP/HLTF/p62/mTOR axis may be a new oncogenic driver involved in HCC development. This finding provides a potential therapeutic strategy for HCC patients by targeting the β-TrCP/HLTF/p62/mTOR axis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/jmcb/mjad012 |
| DOI: | 10.1093/jmcb/mjad012/49320092/mjad012.pdf |
| الإتاحة: | https://doi.org/10.1093/jmcb/mjad012Test https://academic.oup.com/jmcb/article-pdf/15/2/mjad012/51724151/mjad012.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.7E38A847 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/jmcb/mjad012 |
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