RETRACTED ARTICLE: TRIB2 confers resistance to anti-cancer therapy by activating the serine/threonine protein kinase AKT

• DOI: 10.1038/ncomms14687
• Publication Date: 2017-03-09T10:52:51Z
• Authors: Richard Hill; Patricia A. Madur...; Bibiana Ferreira; Inês Baptista; Susana Machado; Laura Colaço; Marta dos Santos; Ningshu Liu; Ana Dopazo; Selma Ugurel; Angyal Adrienn; Endre Kiss-Toth; Murat Isbilen; Ali O. Gure; Wolfgang Link
• Keywords: Ectopic expression; AKT2

Abstract Intrinsic and acquired resistance to chemotherapy is the fundamental reason for treatment failure many cancer patients. The identification of molecular mechanisms involved in drug or sensitization imperative. Here we report that tribbles homologue 2 (TRIB2) ablates forkhead box O activation disrupts p53/MDM2 regulatory axis, conferring various chemotherapeutics. TRIB2 suppression exerted via direct interaction with AKT a key signalling protein cell proliferation, survival metabolism pathways. Ectopic intrinsic high expression induces by promoting phospho-AKT (at Ser473) its COP1 domain. significantly increased tumour tissues from patients correlating an phosphorylation AKT, FOXO3a, MDM2 impaired therapeutic response. This culminates extremely poor clinical outcome. Our study reveals novel mechanism underlying suggests functions as component PI3K network, activating cells.