The c-MYC-BMI1 axis is essential for SETDB1-mediated breast tumourigenesis.

Autor: Xiao JF; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Sun QY; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Ding LW; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Chien W; Division of Hematology/Oncology, Cedar-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA., Liu XY; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Mayakonda A; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Jiang YY; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Loh XY; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Ran XB; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Doan NB; Department of Pathology, University of California, Los Angeles, CA, USA., Castor B; Department of Pathology, University of California, Los Angeles, CA, USA., Chia D; Departments of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA., Said JW; Department of Pathology, University of California, Los Angeles, CA, USA., Tan KT; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Yang H; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Fu XY; Cancer Science Institute of Singapore, National University of Singapore, Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Lin DC; Division of Hematology/Oncology, Cedar-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA., Koeffler HP; Cancer Science Institute of Singapore, National University of Singapore, Singapore.; Division of Hematology/Oncology, Cedar-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2018 Sep; Vol. 246 (1), pp. 89-102. Date of Electronic Publication: 2018 Aug 03.
DOI: 10.1002/path.5126
Abstrakt: Characterising the activated oncogenic signalling that leads to advanced breast cancer is of clinical importance. Here, we showed that SET domain, bifurcated 1 (SETDB1), a histone H3 lysine 9 methyltransferase, is aberrantly expressed and behaves as an oncogenic driver in breast cancer. SETDB1 enhances c-MYC and cyclin D1 expression by promoting the internal ribosome entry site (IRES)-mediated translation of MYC/CCND1 mRNA, resulting in prominent signalling of c-MYC to promote cell cycle progression, and provides a growth/self-renewal advantage to breast cancer cells. The activated c-MYC-BMI1 axis is essential for SETDB1-mediated breast tumourigenesis, because silencing of either c-MYC or BMI1 profoundly impairs the enhanced growth/colony formation conferred by SETDB1. Furthermore, c-MYC directly binds to the SETDB1 promoter region and enhances its transcription, suggesting a positive regulatory interplay between SETDB1 and c-MYC. In this study, we identified SETDB1 as a prominent oncogene and characterised the underlying mechanism whereby SETDB1 drives breast cancer, providing a therapeutic rationale for targeting SETDB1-BMI1 signalling in breast cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
(Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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