In:
The Journal of Pathology, Wiley, Vol. 246, No. 1 ( 2018-09), p. 89-102
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0022-3417
,
1096-9896
DOI:
10.1002/path.2018.246.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
1475280-3
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