Abstract
Eukaryotic translation initiation factors (eIFs) constitute a new class of therapeutic cancer targets. EIF3b is the major scaffold protein of eIF3 (the largest core of eIFs). We sought to define the role played by and the mechanism of action of eIF3b in patients with clear cell renal cell carcinoma (ccRCC). We found that high-level eIF3b expression in tumors was not only associated with an aggressive tumor phenotype, but was also independently prognostic for patients with ccRCC. Knockdown of eIF3b impaired the action of the Akt pathway, thus inhibiting cell proliferation by disrupting the cell cycle and triggering apoptosis. Furthermore, the epithelial-to-mesenchymal transition was impaired after eIF3b depletion, via suppression of cell migration and invasion. Additionally, eIF3b knockdown significantly inhibited the growth of subcutaneous xenografts in mice. Together, these data show that eIF3b is both a promising prognostic biomarker and a potential therapeutic target for patients with ccRCC.