Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-019-09257-z
Title: Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma
Authors: CHEN YE 
Xu, Liang
Anand Mayakonda Thippeswamy 
Huang, Mo-Li
Kanojia, Deepika
Tan, Tuan Zea 
DAKLE PUSHKAR PRAVIN 
LIN YU-TONG, RUBY 
Ke, Xin-Yu
Said, Jonathan W
Chen, Jianxiang
Gery, Sigal
Ding, L.-W. 
Jiang, Yan-Yi
Pang, Angela
MARK EDWARD PUHAINDRAN 
Boon Cher Goh 
Koeffler, H Phillip
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
E3 UBIQUITIN LIGASE
MYXOID LIPOSARCOMA
SUPER-ENHANCERS
CELL-LINE
DEDIFFERENTIATED LIPOSARCOMA
TLS-CHOP
TRABECTEDIN
CHEMOTHERAPY
SENSITIVITY
INHIBITORS
Issue Date: 22-Mar-2019
Publisher: NATURE PUBLISHING GROUP
Citation: CHEN YE, Xu, Liang, Anand Mayakonda Thippeswamy, Huang, Mo-Li, Kanojia, Deepika, Tan, Tuan Zea, DAKLE PUSHKAR PRAVIN, LIN YU-TONG, RUBY, Ke, Xin-Yu, Said, Jonathan W, Chen, Jianxiang, Gery, Sigal, Ding, L.-W., Jiang, Yan-Yi, Pang, Angela, MARK EDWARD PUHAINDRAN, Boon Cher Goh, Koeffler, H Phillip (2019-03-22). Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma. NATURE COMMUNICATIONS 10 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-019-09257-z
Abstract: Liposarcomas (LPSs) are a group of malignant mesenchymal tumors showing adipocytic differentiation. Here, to gain insight into the enhancer dysregulation and transcriptional addiction in this disease, we chart super-enhancer structures in both LPS tissues and cell lines. We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. Additionally, SNAI2 is identified as a crucial downstream target that enforces both proliferative and metastatic potentials to de-differentiated LPS cells. Genetic depletion of BET genes, core transcriptional factors, or SNAI2 mitigates consistently LPS malignancy. We also reveal a compelling susceptibility of LPS cells to BET protein degrader ARV-825. BET protein depletion confers additional advantages to circumvent acquired resistance to Trabectedin, a chemotherapy drug for LPS. Moreover, this study provides a framework for discovering and targeting of core oncogenic transcriptional programs in human cancers.
Source Title: NATURE COMMUNICATIONS
URI: https://scholarbank.nus.edu.sg/handle/10635/209486
ISSN: 2041-1723
DOI: 10.1038/s41467-019-09257-z
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