CIC bioGUNE
Published September 11, 2020 | Version v1
Journal article Open

Genomic and Functional Regulation of TRIB1 Contributes to Prostate Cancer Pathogenesis

Authors/Creators

  • 1. CIC bioGUNE, Derio, Spain
  • 2. Medicine and Surgery Department, Veterinary Faculty, Complutense University of Madrid
  • 3. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK
  • 4. Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Spain
  • 5. Biochemistry and Molecular Biology Department, Complutense University of Madrid, 28040 Madrid, Spain

Description

Prostate cancer is the most frequent malignancy in European men and the second worldwide. One of the major oncogenic events in this disease includes amplification of the transcription factor cMYC. Amplification of this oncogene in chromosome 8q24 occurs concomitantly with the copy number increase in a subset of neighboring genes and regulatory elements, but their contribution to disease pathogenesis is poorly understood. Here we show that TRIB1 is among the most robustly upregulated coding genes within the 8q24 amplicon in prostate cancer. Moreover, we demonstrate that TRIB1 amplification and overexpression are frequent in this tumor type. Importantly, we find that, parallel to its amplification, TRIB1 transcription is controlled by cMYC. Mouse modeling and functional analysis revealed that aberrant TRIB1 expression is causal to prostate cancer pathogenesis. In sum, we provide unprecedented evidence for the regulation and function of TRIB1 in prostate cancer.

Files

2020 Shahrouzi Cancers.pdf

Files (3.0 MB)

Name Size Download all
md5:b70431ed950934b34e4ba9715a927bbf
3.0 MB Preview Download

Additional details

Funding

European Commission
CANCERMETAB - Metabolic requirements for prostate cancer cell fitness 336343
European Commission
CancerADAPT - Targeting the adaptive capacity of prostate cancer through the manipulation of transcriptional and metabolic traits 819242