RT Journal Article
T1 The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer
A1 Orea Soufi, Alba
A1 Castillo Lluva, Sonia
A1 Salvador Tormo, Nélida
A1 Martín Cabrera, Paola
A1 Recuero, Silvia
A1 Gabicagogeascoa, Estíbaliz
A1 Moreno Valladares, Manuel
A1 Mendiburu-Eliçabe Garganta, Marina
A1 Blanco Gómez, Adrián
A1 Ramos Pittol, José Miguel
A1 García Taboada, Elena
A1 Ocaña, Alberto
A1 Cimas, Francisco J.
A1 Matheu, Ander
A1 Álvarez López, Isabel
A1 Velasco, Guillermo
A1 Lorente, Mar
AB 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 bioinformatic analyses in public datasets. Results: TRIB3 enhanced the proliferation and AKT phosphorylation 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.
PB MDPI
SN 2072-6694
YR 2021
FD 2021-10-22
LK https://hdl.handle.net/20.500.14352/4916
UL https://hdl.handle.net/20.500.14352/4916
LA eng
NO Unión Europea. Horizonte 2020
NO Ministerio de Economía y Competitividad (MINECO) / FEDER
NO Instituto de Salud Carlos III (ISCIII) / Fondo de Desarrollo Regional Europeo (FDRE)
NO Breast Cancer Now Foundation
DS Docta Complutense
RD 24 dic 2025