Please use this identifier to cite or link to this item: https://doi.org/10.1002/path.4773
Title: P/CAF mediates PAX3–FOXO1-dependent oncogenesis in alveolar rhabdomyosarcoma
Authors: Bharathy, Narendra
Suriyamurthy, Sudha
Rao, Vinay Kumar
Ow, Jin Rong
Lim, Huey Jin
Chakraborty, Payal
Vasudevan, Madavan
Dhamne, Chetan Anil
Chang, Kenneth Tou En
VICTOR LEE KWAN MIN 
Kundu, Tapas K
RESHMA TANEJA 
Keywords: cancer
epigenetics
histone acetyltransferase
post-translational modifications
stability
Animals
Carcinogenesis
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Epigenomics
Gene Silencing
Heterografts
Mice
Mice, Nude
Muscles
MyoD Protein
Oligonucleotide Array Sequence Analysis
Oncogene Proteins, Fusion
Paired Box Transcription Factors
Rhabdomyosarcoma, Alveolar
Signal Transduction
p300-CBP Transcription Factors
Gene Expression Regulation, Neoplastic
Protein Processing, Post-Translational
Issue Date: 1-Nov-2016
Publisher: Wiley
Citation: Bharathy, Narendra, Suriyamurthy, Sudha, Rao, Vinay Kumar, Ow, Jin Rong, Lim, Huey Jin, Chakraborty, Payal, Vasudevan, Madavan, Dhamne, Chetan Anil, Chang, Kenneth Tou En, VICTOR LEE KWAN MIN, Kundu, Tapas K, RESHMA TANEJA (2016-11-01). P/CAF mediates PAX3–FOXO1-dependent oncogenesis in alveolar rhabdomyosarcoma. The Journal of Pathology 240 (3) : 269-281. ScholarBank@NUS Repository. https://doi.org/10.1002/path.4773
Abstract: Alveolar rhabdomyosarcoma (ARMS) is an aggressive paediatric cancer of skeletal muscle with poor prognosis. A PAX3-FOXO1 fusion protein acts as a driver of malignancy in ARMS by disrupting tightly coupled but mutually exclusive pathways of proliferation and differentiation. While PAX3-FOXO1 is an attractive therapeutic target, no current treatments are designed to block its oncogenic activity. The present work shows that the histone acetyltransferase P/CAF (KAT2B) is overexpressed in primary tumours from ARMS patients. Interestingly, in fusion-positive ARMS cell lines, P/CAF acetylates and stabilizes PAX3-FOXO1 rather than MyoD, a master regulator of muscle differentiation. Silencing P/CAF, or pharmacological inhibition of its acetyltransferase activity, down-regulates PAX3-FOXO1 levels concomitant with reduced proliferation and tumour burden in xenograft mouse models. Our studies identify a P/CAF-PAX3-FOXO1 signalling node that promotes oncogenesis and may contribute to MyoD dysfunction in ARMS. This work exemplifies the therapeutic potential of targeting chromatin-modifying enzymes to inhibit fusion oncoproteins that are a frequent event in sarcomas. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Source Title: The Journal of Pathology
URI: http://scholarbank.nus.edu.sg/handle/10635/137823
ISSN: 00223417
DOI: 10.1002/path.4773
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
2016-PCAF_mediates_dependent_oncogenesis-postprint.pdf2 MBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

5
checked on Dec 12, 2018

WEB OF SCIENCETM
Citations

4
checked on Dec 12, 2018

Page view(s)

38
checked on Dec 6, 2018

Download(s)

13
checked on Dec 6, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.