Embryonic T-box transcription factor Brachyury: Dissecting its role in prostate cancer biology and clinical application

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men and therapy resistance is a major problem for PCa patients. Recently, we identified Brachyury as a new biomarker of PCa aggressiveness and poor prognosis, and demonstrated that this transcription factor is a direct regulator of androgen receptor expression, contributing to tumor chemotherapy resistance and constituting an attractive target for advanced PCa. Since the successful therapy of patients with PCa is highly dependent on reliable diagnostic and prognostic biomarkers, we aim to dissect the molecular mechanisms through which Brachyury is modulating therapeutic response, discover the network of genes and pathways regulated by Brachyury, and finally to develop a chip RNA-based platform to detect Brachyury, its targets and other major known prostate biomarkers, which could constitute a tool for early diagnosis and potentially therapeutic prediction in PCa patients using non-invasive liquid biopsy.

Funding Agency

FCT / FEDER

Project Reference

PTDC/MED-ONC/31423/2017

Project Members

Rui M. Reis

Principal Investigator Project Leader

Olga Martinho

Affiliated Researcher

Adriana Mendes

PhD Student

Patrícia Fontão

PhD Student

Main Project Outcomes

Inês Lages, “Dissecting chemotherapy resistance in prostate cancer: Interplay between RKIP and Brachyury proteins.”, Master in Health Sciences, University of Minho, June 2019.

Patricia Fontão, “Embryonic T-box transcription factor Brachyury as a predictive biomarker and therapeutic target in prostate and lung cancers.” Master in Applied Biochemistry, University of Minho, March 2021.

Cardoso-Carneiro D, Raquel-Cunha A, Pinheiro J, Gabriela-Freitas M, Fontão P, Reis RM, Martinho O. Implications of RKIP protein in cancer prognosis and therapy response: a literature update. In “Prognostic and Therapeutic Applications of RKIP in Cancer”, Chapter 20, Bonavida B. & Baritaki S., Elsevier. 2020. Pages 389-414

Gabriela-Freitas M, Pinheiro J, Raquel-Cunha A, Cardoso-Carneiro D, Martinho O. RKIP as an Inflammatory and Immune System Modulator: Implications in Cancer. Biomolecules 2019, 9, 769.

Pinto F, Costa AM, Santos GC, Matsushita MM, Costa S, Silva VA, Miranda-Gonçalves V, Lopes CM, Clara CA, Becker AP, Neder L, Hajj GN, da Cunha IW, Jones C, Andrade RP, Reis RM. The T-box transcription factor brachyury behaves as a tumor suppressor in gliomas. J Pathol.2020 May;251(1):87-99.

Pinto F, Costa ÂM, Andrade RP, Reis RM. Brachyury Is Associated with Glioma Differentiation and Response to Temozolomide. Neurotherapeutics. 2020 Oct;17(4):2015-2027.

Rui Manuel Reis, Dr Jekyll and Mr Hyde: The strange case of Brachyury in cancer, BRAGFOST – Munich, 5- 8 September, 2019.

Olga Martinho: Raf Kinase Inhibitory Protein (RKIP): a new predictor of EGFR targeted therapy response in solid tumors?. VII International Symposium on Translational Oncology, 13 to 14 September 2019, Hospital de Câncer de Barretos, Brazil.