Abstract
Although overexpression of the eukaryotic translation initiation factor 4E (eIF4E) is detected in patients with renal cell carcinoma (RCC) and associated with poor prognosis, the possible roles of eIF4E in RCC have not been revealed. The effects of eIF4E inhibition on cell growth, migration, survival, chemo-/immunotherapy and eIF4E pathways via pharmacological inhibitor and genetic siRNA knockdown were analyzed in RCC cells. In this work, we demonstrate that eIF4E is critically involved in multiple biological functions of RCC. We firstly inhibited eIF4E activity by ribavirin in two cell lines (Caki-1 and ACHN) representing RCC metastasis models. We demonstrated that ribavirin inhibited proliferation and migration and induced apoptosis in RCC in a dose-dependent manner. We further confirmed that the inhibitory effects of ribavirin were attributed to its ability in inhibiting eIF4E-regulated protein translation and activity. eIF4E inhibition using siRNA knockdown mimicked ribavirin's effector in RCC cells. Importantly, eIF4E inhibition by both ribavirin and siRNA knockdown significantly sensitized RCC response to chemo- and immunotherapeutic agents in vitro as well as in vivo. Our findings clearly demonstrate the roles of eIF4E i...Continue Reading
References
Jul 1, 1993·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·L M MinasianS E Krown
Mar 22, 2002·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Shane CrottyRaul Andino
Feb 21, 2004·Blood·Michael G KharasDavid A Fruman
Aug 18, 2004·Genes & Development·Nissim Hay, Nahum Sonenberg
Dec 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Alex KentsisKatherine L B Borden
Oct 28, 2005·RNA·Alex KentsisKatherine L B Borden
Feb 22, 2007·PloS One·Yaël MamaneNahum Sonenberg
Jul 20, 2007·Cancer Research·Ola LarssonVitaly A Polunovsky
Dec 7, 2007·Genes & Development·Hans-Guido WendelScott W Lowe
Aug 19, 2008·Biochemical and Biophysical Research Communications·Keith TanKatherine L B Borden
May 13, 2009·Blood·Sarit AssoulineKatherine L B Borden
Mar 19, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Filippa PetterssonWilson H Miller
Apr 2, 2011·Leukemia·B C KraljacicK Borden
Aug 11, 2011·Current Clinical Pharmacology·Toni K Choueiri
Mar 5, 2015·Oncology Reports·Erick De la Cruz-HernandezAlfonso Dueñas-Gonzalez
Mar 7, 2015·Nature Reviews. Drug Discovery·Mamatha BhatIvan Topisirovic
Sep 1, 2015·PloS One·Fangfang ShiTianyou Yan
Jan 26, 2016·World Journal of Hepatology·Véronique Loustaud-RattiPaul Carrier
Jun 12, 2016·Cellular Signalling·Michal GrzmilBrian A Hemmings
Dec 10, 2016·Biochemical and Biophysical Research Communications·Dehua DaiYi Tang
Dec 21, 2016·Molecular Cancer·Klaudia K BrodaczewskaAnna M Czarnecka
May 30, 2017·Urologic Oncology·Alp Tuna BeksacKetan K Badani
Jul 12, 2017·Nature Reviews. Nephrology·Edwin M PosadasRobert A Figlin
Aug 15, 2017·Urologic Oncology·Ahmet BindayiIthaar H Derweesh
Citations
Jul 7, 2020·BioMed Research International·Dehong ChenJun Cao
Jul 25, 2020·Experimental Cell Research·Yan-Song ZhengYingchun Liu
Aug 25, 2020·The American Journal of the Medical Sciences·Jun CaoDehong Chen
Feb 12, 2019·Biochemical and Biophysical Research Communications·Jing JinAli Deng
Sep 3, 2021·Cancer Research·Michaël CerezoShensi Shen