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Date publication
janvier 2023
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DESAUBRY Laurent
Tous les auteurs :
Steinmann SM, Sánchez-Martín A, Tanzer E, Cigliano A, Pes GM, Simile MM, Desaubry L, Marin JJG, Evert M, Calvisi DF
Lien Pubmed
Résumé
Hepatocellular carcinoma (HCC) is a primary liver tumor with high lethality and increasing incidence worldwide. While tumor resection or liver transplantation is effective in the early stages of the disease, the therapeutic options for advanced HCC remain limited and the benefits are temporary. Thus, novel therapeutic targets and more efficacious treatments against this deadly cancer are urgently needed. Here, we investigated the pathogenetic and therapeutic role of eukaryotic initiation factor 4A1 (eIF4A1) in this tumor type. We observed consistent eIF4A1 upregulation in HCC lesions compared with non-tumorous surrounding liver tissues. In addition, levels were negatively correlated with the prognosis of HCC patients. In HCC lines, the exposure to various eIF4A inhibitors triggered a remarkable decline in proliferation and augmented apoptosis, paralleled by the inhibition of several oncogenic pathways. Significantly, anti-growth effects were achieved at nanomolar concentrations of the eIF4A1 inhibitors and were further increased by the simultaneous administration of the pan mTOR inhibitor, Rapalink-1. In conclusion, our results highlight the pathogenetic relevance of eIF4A1 in HCC and recommend further evaluation of the potential usefulness of pharmacological combinations based on eIF4A and mTOR inhibitors in treating this aggressive tumor.
Mots clés
eIF4A1, hepatocellular carcinoma, targeted therapies, translation inhibitors
Référence
Int J Mol Sci. 2023 01 20;24(3):
