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Background <p>Globally, among gynecological malignancies, ovarian cancer (OC) stands as an important factor contributing to mortality. E3 ubiquitin ligase activity is a common characteristic found in the tripartite motif (TRIM) proteins, contributing significantly to post-translational modifications of various proteins. Among these TRIM proteins, TRIM15 has been linked to multiple cancer types. Nevertheless, the function of TRIM15 concerning OC has yet to be elucidated. We aimed to explore the role of TRIM15 in OC and shed light on the underlying mechanisms thereof.</p> Methods <p>A bioinformatics analysis was conducted to investigate the variance in TRIM15 expression between normal ovarian tissues and OC tissues, and to explore the prognostic significance of TRIM15 in patients with OC. TRIM15 protein expression in OC tissues was detected using immunofluorescence. The impact of TRIM15 silencing and overexpression on the proliferation and migration of OC cells was assessed through various functional experiments, such as CCK-8, colony formation, and Transwell assays. Mass spectrometry analysis was performed to identify TRIM15-interacting substrates. The mechanism underlying substrate ubiquitination mediated by TRIM15 was further explored.</p> Results <p>Based on The Cancer Genome Atlas (TCGA) data and immunofluorescence analysis, OC tissues exhibited significant upregulation of TRIM15 expression. si-RNA-mediated silencing of TRIM15 suppressed the in vitro proliferation and migration of OVCAR3 and A2780 cells. Paxillin was selected as an interacting protein with TRIM15 by mass spectrometry. Mechanically, we discovered that TRIM15 mediated the ubiquitination of Paxillin via Lys11- and Lys29-linked polyubiquitin chains. Subsequent co-IP experiments revealed that TRIM15 could also enhance the interactions between Paxillin and its tyrosine kinase, FAK, thereby promoting the phosphorylation of Paxillin.</p> Conclusions <p>We revealed a previously unknown mechanism by which TRIM15 ubiquitinates and phosphorylates Paxillin to promote OC progression. These findings suggest that targeting TRIM15 holds promise as a therapeutic approach to treat OC.</p>

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TRIM15 Mediates ubiquitination of Paxillin to facilitate the progression of ovarian cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月26日

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  • Jiaqi Xu,
  • Tiantian Wu,
  • Fei Wu,
  • Yue Zhu,
  • Meng Liu,
  • Yan Zhang,
  • Wenxin Gao,
  • Weifeng Qian,
  • Guannan Feng,
  • Xiaoyan Huang,
  • Xiaoxue Xi,
  • Shunyu Hou

摘要

Background

Globally, among gynecological malignancies, ovarian cancer (OC) stands as an important factor contributing to mortality. E3 ubiquitin ligase activity is a common characteristic found in the tripartite motif (TRIM) proteins, contributing significantly to post-translational modifications of various proteins. Among these TRIM proteins, TRIM15 has been linked to multiple cancer types. Nevertheless, the function of TRIM15 concerning OC has yet to be elucidated. We aimed to explore the role of TRIM15 in OC and shed light on the underlying mechanisms thereof.

Methods

A bioinformatics analysis was conducted to investigate the variance in TRIM15 expression between normal ovarian tissues and OC tissues, and to explore the prognostic significance of TRIM15 in patients with OC. TRIM15 protein expression in OC tissues was detected using immunofluorescence. The impact of TRIM15 silencing and overexpression on the proliferation and migration of OC cells was assessed through various functional experiments, such as CCK-8, colony formation, and Transwell assays. Mass spectrometry analysis was performed to identify TRIM15-interacting substrates. The mechanism underlying substrate ubiquitination mediated by TRIM15 was further explored.

Results

Based on The Cancer Genome Atlas (TCGA) data and immunofluorescence analysis, OC tissues exhibited significant upregulation of TRIM15 expression. si-RNA-mediated silencing of TRIM15 suppressed the in vitro proliferation and migration of OVCAR3 and A2780 cells. Paxillin was selected as an interacting protein with TRIM15 by mass spectrometry. Mechanically, we discovered that TRIM15 mediated the ubiquitination of Paxillin via Lys11- and Lys29-linked polyubiquitin chains. Subsequent co-IP experiments revealed that TRIM15 could also enhance the interactions between Paxillin and its tyrosine kinase, FAK, thereby promoting the phosphorylation of Paxillin.

Conclusions

We revealed a previously unknown mechanism by which TRIM15 ubiquitinates and phosphorylates Paxillin to promote OC progression. These findings suggest that targeting TRIM15 holds promise as a therapeutic approach to treat OC.