The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer
AuthorsOrea-Soufi, Alba; email: firstname.lastname@example.org
Castillo-Lluva, Sonia; orcid: 0000-0001-5357-7178; email: email@example.com
Salvador-Tormo, Nélida; email: firstname.lastname@example.org
Martín-Cabrera, Paola; email: email@example.com
Recuero, Silvia; email: firstname.lastname@example.org
Gabicagogeascoa, Estíbaliz; email: email@example.com
Moreno-Valladares, Manuel; email: MANUEL.MORENOVALLADARES@osakidetza.eus
Mendiburu-Eliçabe, Marina; orcid: 0000-0003-2573-8709; email: firstname.lastname@example.org
Blanco-Gómez, Adrián; orcid: 0000-0002-1956-088X; email: email@example.com
Ramos-Pittol, José Miguel; orcid: 0000-0003-3753-5394; email: Jose.Ramos-Pittol@uibk.ac.at
García-Taboada, Elena; email: firstname.lastname@example.org
Ocaña, Alberto; orcid: 0000-0002-1067-9630; email: email@example.com
Cimas, Francisco J.; email: firstname.lastname@example.org
Matheu, Ander; email: email@example.com
Álvarez-López, Isabel; email: ISABELMANUELA.ALVAREZLOPEZ@osakidetza.eus
Velasco, Guillermo; orcid: 0000-0002-1994-2386; email: firstname.lastname@example.org
Lorente, Mar; orcid: 0000-0003-0982-0956; email: email@example.com
MetadataShow full item record
AbstractBackground: 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.
CitationCancers, volume 13, issue 21, page e5307
DescriptionFrom MDPI via Jisc Publications Router
History: accepted 2021-10-19, pub-electronic 2021-10-22
Publication status: Published
Funder: Instituto de Salud Carlos III; Grant(s): PI18/00442
Funder: European Commission; Grant(s): ITN-308 2016 721532
Funder: Breast Cancer Now; Grant(s): 2012NovSP033
Funder: Ministry of Economy, Industry and Competitiveness; Grant(s): RTI2018-094130-B-100
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