Scholarlink

<p>Ubiquitination is a posttranslational modification that regulates tumour progression-associated proteins through the ubiquitin‒proteasome system, making E3 ligases potential antitumour targets. Here, we report that TRIM8, a member of the TRIM family and an E3 ligase, can act as a tumour suppressor in non-small cell lung cancer (NSCLC). Both gain- and loss-of-function experiments revealed that TRIM8 inhibits the proliferation, colony formation, migration and invasion of NSCLC cells. Experiments with a xenograft model showed that TRIM8 expression suppresses tumour metastasis in vivo. Moreover, low expression of TRIM8 was associated with poor overall survival in both the Taiwanese and GEO lung cancer cohorts. TRIM8 overexpression in lung cancer cells reduced MYOF expression, and restoring MYOF rescued cell migration in TRIM8-overexpressing cells. TRIM8 targeted MYOF for K48-linked ubiquitination, facilitating proteasome-mediated degradation and subsequently suppressing the extracellular secretion of MMPs. Our results provide new insights into the contribution of TRIM8 to lung cancer progression, suggesting that TRIM8 is a new biomarker and a novel therapeutic target for lung cancer.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

E3 ligase TRIM8 suppresses lung cancer metastasis by targeting MYOF degradation through K48-linked polyubiquitination

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月11日

查看全文
  • Chi-Hsuan Wei,
  • Chia-Wei Weng,
  • Chih-Ying Wu,
  • Hsuan-Yu Chen,
  • Ya-Hsuan Chang,
  • Gee-Chen Chang,
  • Jeremy J. W. Chen

摘要

Ubiquitination is a posttranslational modification that regulates tumour progression-associated proteins through the ubiquitin‒proteasome system, making E3 ligases potential antitumour targets. Here, we report that TRIM8, a member of the TRIM family and an E3 ligase, can act as a tumour suppressor in non-small cell lung cancer (NSCLC). Both gain- and loss-of-function experiments revealed that TRIM8 inhibits the proliferation, colony formation, migration and invasion of NSCLC cells. Experiments with a xenograft model showed that TRIM8 expression suppresses tumour metastasis in vivo. Moreover, low expression of TRIM8 was associated with poor overall survival in both the Taiwanese and GEO lung cancer cohorts. TRIM8 overexpression in lung cancer cells reduced MYOF expression, and restoring MYOF rescued cell migration in TRIM8-overexpressing cells. TRIM8 targeted MYOF for K48-linked ubiquitination, facilitating proteasome-mediated degradation and subsequently suppressing the extracellular secretion of MMPs. Our results provide new insights into the contribution of TRIM8 to lung cancer progression, suggesting that TRIM8 is a new biomarker and a novel therapeutic target for lung cancer.