Steinmann, Sara M. and Sanchez-Martin, Anabel and Tanzer, Elisabeth and Cigliano, Antonio and Pes, Giovanni M. and Simile, Maria M. and Desaubry, Laurent and Marin, Jose J. G. and Evert, Matthias and Calvisi, Diego F. (2023) eIF4A1 Is a Prognostic Marker and Actionable Target in Human Hepatocellular Carcinoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (3): 2055. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
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, eIF4A1 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EUKARYOTIC TRANSLATION INITIATION; EXPRESSION; SORAFENIB; PREDICTS; FAMILY; hepatocellular carcinoma; translation inhibitors; targeted therapies |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2024 08:37 |
| Last Modified: | 23 Mar 2024 08:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60299 |
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