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1.	Chan, K, et al. (author) eIF4A supports an oncogenic translation program in pancreatic ductal adenocarcinoma 2019 In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5151- Journal article (peer-reviewed)abstract Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with limited treatment options. Although metabolic reprogramming is a hallmark of many cancers, including PDA, previous attempts to target metabolic changes therapeutically have been stymied by drug toxicity and tumour cell plasticity. Here, we show that PDA cells engage an eIF4F-dependent translation program that supports redox and central carbon metabolism. Inhibition of the eIF4F subunit, eIF4A, using the synthetic rocaglate CR-1-31-B (CR-31) reduced the viability of PDA organoids relative to their normal counterparts. In vivo, CR-31 suppresses tumour growth and extends survival of genetically-engineered murine models of PDA. Surprisingly, inhibition of eIF4A also induces glutamine reductive carboxylation. As a consequence, combined targeting of eIF4A and glutaminase activity more effectively inhibits PDA cell growth both in vitro and in vivo. Overall, our work demonstrates the importance of eIF4A in translational control of pancreatic tumour metabolism and as a therapeutic target against PDA.
2.	Hulea, L, et al. (author) Translational and HIF-1α-Dependent Metabolic Reprogramming Underpin Metabolic Plasticity and Responses to Kinase Inhibitors and Biguanides 2018 In: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 28:6, s. 817- Journal article (peer-reviewed)
3.	Morita, M, et al. (author) mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation 2013 In: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 18:5, s. 698-711 Journal article (peer-reviewed)

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Type of publication: journal article (3)

Type of content: peer-reviewed (3)

Author/Editor: Larsson, O (3); Pollak, M (3); Avizonis, D (3); Topisirovic, I (2); Morita, M. (2); McLaughlan, S (2); show more...; Gravel, SP (2); St-Pierre, J (2); Chan, K. (1); Park, J (1); Zheng, L (1); Pelletier, J (1); Robert, F (1); Ferreira, T (1); Yao, M (1); Muller, W (1); Gutierrez, J. (1); Gandin, V (1); Sonenberg, N (1); Lavoie, C. (1); Siegel, P. (1); Oertlin, C (1); Kapeller-Libermann, ... (1); Handly-Santana, A (1); Doubrovin, M (1); Schoepfer, C (1); Da Silva, B (1); Gorton, F (1); Shi, JW (1); Thomas, CJ (1); Brown, LE (1); Porco, JA (1); Chio, IIC (1); Alain, T (1); Gottlieb, E (1); Greenwood, C. (1); Jones, RG (1); Cargnello, M (1); Hulea, L (1); Sikstrom, K (1); Ohh, M (1); Ursini-Siegel, J (1); Uchenunu, O (1); Im, YK (1); Lehuede, C (1); Ma, EH (1); Leibovitch, M (1); Blouin, MJ (1); Parisotto, M (1); Papavasiliou, V (1); show less...

University: Karolinska Institutet (3)

Language: English (3)

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