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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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/21/5307 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:05:21Z |
| format | Article |
| id | doaj.art-2ddfb020abf5403b9f645cb2a10c2e8d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:05:21Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2ddfb020abf5403b9f645cb2a10c2e8d2023-11-22T20:33:18ZengMDPI AGCancers2072-66942021-10-011321530710.3390/cancers13215307The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast CancerAlba Orea-Soufi0Sonia Castillo-Lluva1Nélida Salvador-Tormo2Paola Martín-Cabrera3Silvia Recuero4Estíbaliz Gabicagogeascoa5Manuel Moreno-Valladares6Marina Mendiburu-Eliçabe7Adrián Blanco-Gómez8José Miguel Ramos-Pittol9Elena García-Taboada10Alberto Ocaña11Francisco J. Cimas12Ander Matheu13Isabel Álvarez-López14Guillermo Velasco15Mar Lorente16Department of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainOsakidetza Basque Health Service, Donostia University Hospital, 20014 San Sebastian, SpainDepartment of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainInstituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca/CSIC, 37007 Salamanca, SpainInstitute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, AustriaDepartment of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainExperimental Therapeutics Unit, Hospital Clínico San Carlos (HCSC), Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040 Madrid, SpainTranslational Research Unit, Translational Oncology Laboratory, Albacete University Hospital, Universidad de Castilla La Mancha (UCLM), 13071 Albacete, SpainDepartment of Oncology, Biodonostia Health Research Institute, 20014 San Sebastián, SpainOsakidetza Basque Health Service, Donostia University Hospital, 20014 San Sebastian, SpainDepartment of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, School of Biology, Complutense University, 28040 Madrid, SpainBackground: 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.https://www.mdpi.com/2072-6694/13/21/5307TRIB3Luminal breast cancerHER2AKTtissue microarrayscell signaling |
| spellingShingle | 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 Cancers TRIB3 Luminal breast cancer HER2 AKT tissue microarrays cell signaling |
| title | 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_short | 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 |
| topic | TRIB3 Luminal breast cancer HER2 AKT tissue microarrays cell signaling |
| url | https://www.mdpi.com/2072-6694/13/21/5307 |
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