RT Journal Article
T1 Loss of Tribbles pseudokinase-3 promotes Akt-driven tumorigenesis via FOXO inactivation
A1 Salazar Roa, María
A1 Lorente Pérez, María Del Mar
A1 Garcia-Taboada, Elena
A1 Pérez Gómez, Eduardo
A1 Davila, Davila
A1 Zuñiga, Patricia
A1 Flores Landeira, Juana María
A1 Rodriguez, Antonio
A1 Hegedus, Zoltán
A1 Mosen-Ansorena, David
A1 Aransay, Ana María
A1 Hernandez-Tiedra, Sonia
A1 Lopez-Valero, Israël
A1 Quintanilla, Miguel
A1 Sánchez García, María Cristina
A1 Iovanna, Juan
A1 Dusetti, Nelson
A1 Guzmán Pastor, Manuel
A1 Francis, Sheila
A1 Carracedo, Arkaitz
A1 Kiss-Toth, Endre
A1 Velasco Díez, Guillermo
AB Tribbles pseudokinase-3 (TRIB3) has been proposed to act as an inhibitor of AKT although the precise molecular basis of this activity and whether the loss of TRIB3 contributes to cancer initiation and progression remain to be clarified. In this study, by using a wide array of in vitro and in vivo approaches, including a Trib3 knockout mouse, we demonstrate that TRIB3 has a tumor- suppressing role. We also find that the mechanism by which TRIB3 loss enhances tumorigenesis relies on the dysregulation of the phosphorylation of AKT by the mTORC2 complex, which leads to an enhanced phosphorylation of AKT on Ser473 and the subsequent hyperphosphorylation and inactivation of the transcription factor FOXO3. These observations support the notion that loss of TRIB3 is associated with a more aggressive phenotype in various types of tumors by enhancing the activity of the mTORC2/AKT/FOXO axis
PB Nature Publishing Group
SN 1350-9047
YR 2014
FD 2014
LK https://hdl.handle.net/20.500.14352/96199
UL https://hdl.handle.net/20.500.14352/96199
LA eng
NO Salazar, M., Lorente, M., García-Taboada, E. et al. Loss of Tribbles pseudokinase-3 promotes Akt-driven tumorigenesis via FOXO inactivation. Cell Death Differ 22, 131–144 (2015). https://doi.org/10.1038/cdd.2014.133
NO This work was supported by grants from Spanish Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) (PS09/01401; PI12/02248, FR2009-0052 and IT2009-0053toGV), Comunidad de Madrid (S2011/BMD-2308toMG), Fundacion Mutua Madrilena (AP101042012 to GV) and Breast Cancer Campaign (2012NovSP033 to EKT and GV). Purchase of the TRIB3-deficient mice (LEXKO-1947) linewas fundedby theWellcomeTrust.
NO Comunidad de Madrid
NO Ministerio de Economía y Competitividad (España)
NO European Commission
NO Fundación Mutua Madrileña
NO Breast Cancer Campaign
DS Docta Complutense
RD 17 abr 2025