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Background <p>Translational reprogramming enables cancer cells to drive tumour progression and metastasis. eIF3i is a core component of the translational regulatory machinery, but the underlying mechanisms through which it promotes tumour metastasis remain unclear.</p> Methods <p>Proteomic analysis identified eIF3i-regulated targets. Functional validation utilised in vitro and in vivo models, including migration/invasion assays, polysome profiling, RNA-binding assays (RIP and RNA pull-down), and mouse metastatic models. Clinical relevance was assessed in CRC patients with liver metastases.</p> Results <p>eIF3i was significantly overexpressed in metastatic CRC. Its knockdown inhibited cell migration, invasion, epithelial-mesenchymal transition (EMT), invadopodia formation in vitro, and lung metastasis in vivo. NELFCD was identified as a key downstream target, whose translation is directly promoted by eIF3i binding to its mRNA, independent of transcription. NELFCD knockdown phenocopied the anti-metastatic effects of eIF3i depletion. Crucially, the pro-metastatic capacity of eIF3i overexpression was abolished by concurrent NELFCD knockdown. eIF3i and NELFCD protein levels showed a significant positive correlation in clinical CRC metastases.</p> Conclusions <p>The eIF3i-NELFCD axis drives CRC metastasis by directly upregulating NELFCD translation, thereby facilitating EMT and invadopodia formation. This pathway represents a promising therapeutic target for inhibiting metastatic progression in CRC.</p>

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eIF3i facilitates NELFCD translation to promote metastasis via regulating EMT and invadopodia

  • 期刊论文

  • 发表日期：

    2025年11月28日

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  • Qing Huang,
  • Juan Zhao,
  • Yang Zhang,
  • Ying Zhou,
  • Xuyang Yang,
  • Xiaoting Chen,
  • Mingtian Wei,
  • Junhong Han,
  • Yaguang Zhang

摘要

Background

Translational reprogramming enables cancer cells to drive tumour progression and metastasis. eIF3i is a core component of the translational regulatory machinery, but the underlying mechanisms through which it promotes tumour metastasis remain unclear.

Methods

Proteomic analysis identified eIF3i-regulated targets. Functional validation utilised in vitro and in vivo models, including migration/invasion assays, polysome profiling, RNA-binding assays (RIP and RNA pull-down), and mouse metastatic models. Clinical relevance was assessed in CRC patients with liver metastases.

Results

eIF3i was significantly overexpressed in metastatic CRC. Its knockdown inhibited cell migration, invasion, epithelial-mesenchymal transition (EMT), invadopodia formation in vitro, and lung metastasis in vivo. NELFCD was identified as a key downstream target, whose translation is directly promoted by eIF3i binding to its mRNA, independent of transcription. NELFCD knockdown phenocopied the anti-metastatic effects of eIF3i depletion. Crucially, the pro-metastatic capacity of eIF3i overexpression was abolished by concurrent NELFCD knockdown. eIF3i and NELFCD protein levels showed a significant positive correlation in clinical CRC metastases.

Conclusions

The eIF3i-NELFCD axis drives CRC metastasis by directly upregulating NELFCD translation, thereby facilitating EMT and invadopodia formation. This pathway represents a promising therapeutic target for inhibiting metastatic progression in CRC.