{"entity": "publication", "iuid": "14963c11419e4c688f2fb859d65b81ad", "timestamp": "2026-09-03T06:02:16.373Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/14963c11419e4c688f2fb859d65b81ad.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/14963c11419e4c688f2fb859d65b81ad"}}, "title": "Translational and HIF-1\u03b1-Dependent Metabolic Reprogramming Underpin Metabolic Plasticity and Responses to Kinase Inhibitors and Biguanides.", "authors": [{"family": "Hulea", "given": "Laura", "initials": "L"}, {"family": "Gravel", "given": "Simon-Pierre", "initials": "SP"}, {"family": "Morita", "given": "Masahiro", "initials": "M"}, {"family": "Cargnello", "given": "Marie", "initials": "M"}, {"family": "Uchenunu", "given": "Oro", "initials": "O"}, {"family": "Im", "given": "Young Kyuen", "initials": "YK"}, {"family": "Lehu\u00e9d\u00e9", "given": "Camille", "initials": "C"}, {"family": "Ma", "given": "Eric H", "initials": "EH"}, {"family": "Leibovitch", "given": "Matthew", "initials": "M"}, {"family": "McLaughlan", "given": "Shannon", "initials": "S"}, {"family": "Blouin", "given": "Marie-Jos\u00e9", "initials": "MJ"}, {"family": "Parisotto", "given": "Maxime", "initials": "M"}, {"family": "Papavasiliou", "given": "Vasilios", "initials": "V"}, {"family": "Lavoie", "given": "Cynthia", "initials": "C"}, {"family": "Larsson", "given": "Ola", "initials": "O"}, {"family": "Ohh", "given": "Michael", "initials": "M"}, {"family": "Ferreira", "given": "Tiago", "initials": "T"}, {"family": "Greenwood", "given": "Celia", "initials": "C"}, {"family": "Bridon", "given": "Ga\u00eblle", "initials": "G"}, {"family": "Avizonis", "given": "Daina", "initials": "D"}, {"family": "Ferbeyre", "given": "Gerardo", "initials": "G"}, {"family": "Siegel", "given": "Peter", "initials": "P"}, {"family": "Jones", "given": "Russell G", "initials": "RG"}, {"family": "Muller", "given": "William", "initials": "W"}, {"family": "Ursini-Siegel", "given": "Josie", "initials": "J"}, {"family": "St-Pierre", "given": "Julie", "initials": "J"}, {"family": "Pollak", "given": "Michael", "initials": "M"}, {"family": "Topisirovic", "given": "Ivan", "initials": "I"}], "type": "journal article", "published": "2018-12-04", "journal": {"title": "Cell Metab.", "issn": "1932-7420", "volume": "28", "issue": "6", "pages": "817-832.e8", "issn-l": "1550-4131"}, "abstract": "There is increasing interest in therapeutically exploiting metabolic differences between normal and cancer cells. We show that kinase inhibitors (KIs) and biguanides synergistically and selectively target a variety of cancer cells. Synthesis of non-essential amino acids (NEAAs) aspartate, asparagine, and serine, as well as glutamine metabolism, are major determinants of the efficacy of KI/biguanide combinations. The mTORC1/4E-BP axis regulates aspartate, asparagine, and serine synthesis by modulating mRNA translation, while ablation of 4E-BP1/2 substantially decreases sensitivity of breast cancer and melanoma cells to KI/biguanide combinations. Efficacy of the KI/biguanide combinations is also determined by HIF-1\u03b1-dependent perturbations in glutamine metabolism, which were observed in VHL-deficient renal cancer cells. This suggests that cancer cells display metabolic plasticity by engaging non-redundant adaptive mechanisms, which allows them to survive therapeutic insults that target cancer metabolism.", "doi": "10.1016/j.cmet.2018.09.001", "pmid": "30244971", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1507297"}, {"db": "pmc", "key": "PMC7252493"}, {"db": "pii", "key": "S1550-4131(18)30566-7"}], "notes": [], "created": "2026-08-20T07:52:43.518Z", "modified": "2026-08-20T07:52:43.568Z"}