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P/CAF mediates PAX3-FOXO1-dependent oncogenesis in alveolar rhabdomyosarcoma

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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


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