dc.contributor.author |
Bharathy, Narendra
|
|
dc.contributor.author |
Suriyamurthy, Sudha
|
|
dc.contributor.author |
Rao, Vinay Kumar
|
|
dc.contributor.author |
Ow, Jin Rong
|
|
dc.contributor.author |
Lim, Huey Jin
|
|
dc.contributor.author |
Chakraborty, Payal
|
|
dc.contributor.author |
Vasudevan, Madavan
|
|
dc.contributor.author |
Dhamne, Chetan Anil
|
|
dc.contributor.author |
Chang, Kenneth Tou En
|
|
dc.contributor.author |
Min, Victor Lee Kwan
|
|
dc.contributor.author |
Kundu, Tapas Kumar
|
|
dc.contributor.author |
Taneja, Reshma
|
|
dc.date.accessioned |
2017-01-24T06:20:41Z |
|
dc.date.available |
2017-01-24T06:20:41Z |
|
dc.date.issued |
2016 |
|
dc.identifier.citation |
Bharathy, N.; Suriyamurthy, S.; Rao, V. K.; Ow, J. R.; Lim, H. J.; Chakraborty, P.; Vasudevan, M.; Dhamne, C. A.; Chang, K. T. E.; Min, V. L. K.; Kundu, T. K.; Taneja, R., P/CAF mediates PAX3-FOXO1-dependent oncogenesis in alveolar rhabdomyosarcoma. Journal of Pathology 2016, 240 (3), 269-281 http://dx.doi.org/10.1002/path.4773 |
en_US |
dc.identifier.citation |
Journal of Pathology |
en_US |
dc.identifier.citation |
240 |
en_US |
dc.identifier.citation |
3 |
en_US |
dc.identifier.issn |
0022-3417 |
|
dc.identifier.uri |
https://libjncir.jncasr.ac.in/xmlui/10572/2087 |
|
dc.description |
Open Access (Accepted Manuscript) |
en_US |
dc.description.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 (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
en_US |
dc.description.uri |
1096-9896 |
en_US |
dc.description.uri |
http://dx.doi.org/10.1002/path.4773 |
en_US |
dc.language.iso |
English |
en_US |
dc.publisher |
Wiley-Blackwell |
en_US |
dc.rights |
@Wiley-Blackwell, 2016 |
en_US |
dc.subject |
Oncology |
en_US |
dc.subject |
Pathology |
en_US |
dc.subject |
cancer |
en_US |
dc.subject |
epigenetics |
en_US |
dc.subject |
histone acetyltransferase |
en_US |
dc.subject |
stability |
en_US |
dc.subject |
post-translational modifications |
en_US |
dc.subject |
Gene-Expression |
en_US |
dc.subject |
Skeletal-Muscle |
en_US |
dc.subject |
Transcriptional Activity |
en_US |
dc.subject |
Malignant Phenotypes |
en_US |
dc.subject |
Signaling Pathway |
en_US |
dc.subject |
Cdna Microarrays |
en_US |
dc.subject |
Target Genes |
en_US |
dc.subject |
In-Vitro |
en_US |
dc.subject |
Pax3-Fkhr |
en_US |
dc.subject |
Embelin |
en_US |
dc.title |
P/CAF mediates PAX3-FOXO1-dependent oncogenesis in alveolar rhabdomyosarcoma |
en_US |
dc.type |
Article |
en_US |