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<p>Gastric cancer remains a significant global health challenge. Lymph node metastasis (LNM) has been identified to be relevant to the prognosis of gastric cancer (GC). However, its mechanisms of progression and metastasis are still not fully understood. Recently, S100A10 has been verified to be aberrantly expressed in various cancers. In this study, we found that S100A10 expression was significantly upregulated in metastatic GC tissues. S100A10 remarkably accelerated tumor metastasis and growth. Mechanistically, dual-luciferase assay and chromatin immunoprecipitation revealed that c-Jun could bind to the promoter region of S100A10 and activate its transcription. Meanwhile, S100A10 competitively bound to Vimentin, preventing it from interacting with ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52), which led to a reduction in K48-linked ubiquitination of vimentin and an increase in vimentin protein levels in GC cells. Subcutaneous xenograft and lung metastasis mouse models were established to prove that targeting inhibition of S100A10 could effectively suppressed tumor metastasis and growth in vivo. In conclusion, S100A10, activated by c-Jun, remarkedly promoted metastasis and proliferation in GC via suppressing vimentin–UBA52 interaction.</p>

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C-Jun-activated S100A10 promotes malignant progression via in diminishing ubiquitin-dependent degradation of vimentin in gastric cancer

  • 期刊论文

  • 发表日期：

    2026年3月6日

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  • Yan Li,
  • Li-xiang Li,
  • Yin-he Sikong,
  • Xiang-dan Cui,
  • Ai-jun Zhang,
  • Xiu-li Zuo

摘要

Gastric cancer remains a significant global health challenge. Lymph node metastasis (LNM) has been identified to be relevant to the prognosis of gastric cancer (GC). However, its mechanisms of progression and metastasis are still not fully understood. Recently, S100A10 has been verified to be aberrantly expressed in various cancers. In this study, we found that S100A10 expression was significantly upregulated in metastatic GC tissues. S100A10 remarkably accelerated tumor metastasis and growth. Mechanistically, dual-luciferase assay and chromatin immunoprecipitation revealed that c-Jun could bind to the promoter region of S100A10 and activate its transcription. Meanwhile, S100A10 competitively bound to Vimentin, preventing it from interacting with ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52), which led to a reduction in K48-linked ubiquitination of vimentin and an increase in vimentin protein levels in GC cells. Subcutaneous xenograft and lung metastasis mouse models were established to prove that targeting inhibition of S100A10 could effectively suppressed tumor metastasis and growth in vivo. In conclusion, S100A10, activated by c-Jun, remarkedly promoted metastasis and proliferation in GC via suppressing vimentin–UBA52 interaction.