The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer

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 b...

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Autores principales:	Alba Orea-Soufi, Sonia Castillo-Lluva, Nélida Salvador-Tormo, Paola Martín-Cabrera, Silvia Recuero, Estíbaliz Gabicagogeascoa, Manuel Moreno-Valladares, Marina Mendiburu-Eliçabe, Adrián Blanco-Gómez, José Miguel Ramos-Pittol, Elena García-Taboada, Alberto Ocaña, Francisco J. Cimas, Ander Matheu, Isabel Álvarez-López, Guillermo Velasco, Mar Lorente
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	TRIB3 Luminal breast cancer HER2 AKT tissue microarrays cell signaling Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/2ddfb020abf5403b9f645cb2a10c2e8d
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spelling	oai:doaj.org-article:2ddfb020abf5403b9f645cb2a10c2e8d2021-11-11T15:27:55ZThe Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer10.3390/cancers132153072072-6694https://doaj.org/article/2ddfb020abf5403b9f645cb2a10c2e8d2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5307https://doaj.org/toc/2072-6694Background: 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.Alba Orea-SoufiSonia Castillo-LluvaNélida Salvador-TormoPaola Martín-CabreraSilvia RecueroEstíbaliz GabicagogeascoaManuel Moreno-ValladaresMarina Mendiburu-EliçabeAdrián Blanco-GómezJosé Miguel Ramos-PittolElena García-TaboadaAlberto OcañaFrancisco J. CimasAnder MatheuIsabel Álvarez-LópezGuillermo VelascoMar LorenteMDPI AGarticleTRIB3Luminal breast cancerHER2AKTtissue microarrayscell signalingNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5307, p 5307 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TRIB3 Luminal breast cancer HER2 AKT tissue microarrays cell signaling Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	TRIB3 Luminal breast cancer HER2 AKT tissue microarrays cell signaling Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Alba Orea-Soufi Sonia Castillo-Lluva Nélida Salvador-Tormo Paola Martín-Cabrera Silvia Recuero Estíbaliz Gabicagogeascoa Manuel Moreno-Valladares Marina Mendiburu-Eliçabe Adrián Blanco-Gómez José Miguel Ramos-Pittol Elena García-Taboada Alberto Ocaña Francisco J. Cimas Ander Matheu Isabel Álvarez-López Guillermo Velasco Mar Lorente The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer
description	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.
format	article
author	Alba Orea-Soufi Sonia Castillo-Lluva Nélida Salvador-Tormo Paola Martín-Cabrera Silvia Recuero Estíbaliz Gabicagogeascoa Manuel Moreno-Valladares Marina Mendiburu-Eliçabe Adrián Blanco-Gómez José Miguel Ramos-Pittol Elena García-Taboada Alberto Ocaña Francisco J. Cimas Ander Matheu Isabel Álvarez-López Guillermo Velasco Mar Lorente
author_facet	Alba Orea-Soufi Sonia Castillo-Lluva Nélida Salvador-Tormo Paola Martín-Cabrera Silvia Recuero Estíbaliz Gabicagogeascoa Manuel Moreno-Valladares Marina Mendiburu-Eliçabe Adrián Blanco-Gómez José Miguel Ramos-Pittol Elena García-Taboada Alberto Ocaña Francisco J. Cimas Ander Matheu Isabel Álvarez-López Guillermo Velasco Mar Lorente
author_sort	Alba Orea-Soufi
title	The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer
title_short	The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer
title_full	The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer
title_fullStr	The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer
title_full_unstemmed	The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer
title_sort	pseudokinase trib3 negatively regulates the her2 receptor pathway and is a biomarker of good prognosis in luminal breast cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2ddfb020abf5403b9f645cb2a10c2e8d
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The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer

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