Src promotes tumor cell invasion by hijacking the translation machineries

Area of Science:

• Molecular oncology
• Cancer cell biology
• Signal transduction

Background:

• The Src oncogene is implicated in cancer cell invasiveness.
• Invadosomes are critical for extracellular matrix (ECM) degradation.
• The eukaryotic translation initiation factor 3 (eIF3) complex is essential for invadosome maintenance.

Purpose of the Study:

• To investigate the role of Src in regulating mRNA translation and its impact on invadosome formation.
• To determine how Src influences eIF3 subunit expression and function.
• To explore the correlation between Src, eIF3 subunits, and hepatocellular carcinoma (HCC) prognosis.

Main Methods:

• Investigated Src's regulation of mRNA translation and eIF3 subunit expression (eIF3h, eIF3e, eIF3d).
• Analyzed Src's modulation of canonical (eIF4E-dependent via PI3K/AKT/mTOR) and non-canonical translation.
• Correlated Src and eIF3h/e/d overexpression with HCC patient prognosis and tumor invasiveness.

Main Results:

• Src regulates mRNA translation and controls expression of key eIF3 subunits (eIF3h, eIF3e, eIF3d).
• Src modulates both canonical and non-canonical translation pathways essential for invadosome function.
• Overexpression of Src and eIF3 subunits correlates with poor HCC prognosis, increased ECM degradation, and tumor invasiveness.

Conclusions:

• Src is a key regulator of translation initiation, impacting invadosome formation and ECM degradation.
• Src-mediated translation control contributes to tumor cell invasion.
• Src and eIF3 subunits serve as potential prognostic markers for HCC.