Suchergebnisse

© 2021 by the authors. ; [Background]: Tribbles pseudokinase 3 (TRIB3) has been proposed to both promote and restrict cancer generation and progression. However, the precise mechanisms that determine this dual role of TRIB3 in cancer remain to be understood. In this study we aimed to investigate the role of TRIB3 in luminal breast cancer, the most frequent subtype of this malignancy. [Methods]: We genetically manipulated TRIB3 expression in a panel of luminal breast cancer cell lines and analyzed its impact on cell proliferation, and the phosphorylation, levels, or subcellular localization of TRIB3 and other protein regulators of key signaling pathways in luminal breast cancer. We also analyzed TRIB3 protein expression in samples from luminal breast cancer patients and performed bioinfor-matic analyses in public datasets. Results: TRIB3 enhanced the proliferation and AKT phosphoryla-tion in luminal A (HER2-) but decreased them in luminal B (HER2+) breast cancer cell lines. TRIB3 negatively regulated the stability of HER2 in luminal B breast cancer cell lines. TRIB3 expression was associated with increased disease-free survival and a better response to therapy in luminal breast cancer patients. [Conclusions]: Our findings support the exploration of TRIB3 as a potential biomarker and therapeutic target in luminal breast cancer. ; This work was funded by the Instituto de Salud Carlos III (ISCIII) and confounded by the European Regional Development Fund (ERDF), "A way to make Europe", grant number PI18/00442 integrated into the State Plan for R & D + I 2017-2020; by the European Commission through the Horizon 2020 European Training Networks program, grant number H2020-MSCA-ITN308 2016 721532; and by the Breast Cancer Now (formerly Breast Cancer Campaign) foundation, grant number 2012NovSP033. Alba Orea-Soufi was supported by a predoctoral FPU contract from Spanish Government. Work in SC-L group is supported by a MINECO/FEDER research grant RTI2018-094130-B-100.