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Essential role of HDAC6 in the regulation of PD-L1 in melanoma

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dc.contributor.author Lienlaf, M.
dc.contributor.author Perez-Villarroel, P.
dc.contributor.author Knox, T.
dc.contributor.author Pabon, M.
dc.contributor.author Sahakian, E.
dc.contributor.author Powers, J.
dc.contributor.author Woan, K.V.
dc.contributor.author Lee, C.
dc.contributor.author Cheng, F.
dc.contributor.author Deng, S.
dc.contributor.author Smalley, K.S.M.
dc.contributor.author Montecino, M.
dc.contributor.author Kozikowski, A.
dc.contributor.author Pinilla-Ibarz, J.
dc.contributor.author Sarnaik, A.
dc.contributor.author Seto, E.
dc.contributor.author Weber, J.
dc.contributor.author Sotomayor, E.M.
dc.contributor.author Villagra, A.
dc.date.accessioned 2017-07-24T15:38:15Z
dc.date.available 2017-07-24T15:38:15Z
dc.date.issued 2016-05
dc.identifier.citation Molecular Oncology Volume 10, Issue 5, 1 May 2016, Pages 735-750 es_CL
dc.identifier.issn 1574-7891
dc.identifier.other DOI: 10.1016/j.molonc.2015.12.012
dc.identifier.uri http://repositorio.unab.cl/xmlui/handle/ria/3764
dc.description Indexación: Web of Science; Scopus. es_CL
dc.description.abstract Histone deacetylases (HDACs), originally described as histone modifiers, have more recently been deMonstrated to target a variety of other proteins unrelated to the chromatin environment. In this context, our present work demonstrates that the pharmacological or genetic abrogation of HDAC6 in primary melanoma samples and cell lines, down-regulates the expression of PD-L1, an important co-stimulatory molecule expressed in cancer cells, which activates the inhibitory regulatory pathway PD-1 in T-cells. Our data suggests that this novel mechanism of PD-L1 regulation is mainly mediated by the influence of HDAC6 over the recruitment and activation of STAT3. Additionally, we observed that selective HDAC6 inhibitors impairs tumor growth and reduce the in vim expression of several inhibitory checkpoint molecules and other regulatory pathways involved in immunosurveillance. Most importantly, these results provide a key pre-clinical rationale and justification to further study isotype selective HDAC6 inhibitors as potential immuno-modulatory agents in cancer. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. es_CL
dc.description.uri http://onlinelibrary.wiley.com/doi/10.1016/j.molonc.2015.12.012/abstract;jsessionid=DB86CF943DA7FD358A75C2CEEAD4D7C4.f03t01
dc.language.iso en es_CL
dc.publisher ELSEVIER SCIENCE es_CL
dc.subject Histone deacetylases es_CL
dc.subject HDAC6 es_CL
dc.subject PD-L1 es_CL
dc.subject STAT3 es_CL
dc.subject PP2A es_CL
dc.subject Melanoma es_CL
dc.subject Nexturastat es_CL
dc.subject Tubastatin A es_CL
dc.title Essential role of HDAC6 in the regulation of PD-L1 in melanoma es_CL
dc.type Article es_CL

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