Kazan Federal University Digital Repository

Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer

Show simple item record

dc.date.accessioned 2019-01-22T20:53:43Z
dc.date.available 2019-01-22T20:53:43Z
dc.date.issued 2018
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/149308
dc.description.abstract © 2018 The Author(s) ARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCCs), diseases that have no effective therapy. Here, we show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers. This correlated with enhanced growth suppression induced by the inhibition of HDAC2 activity in ARID1A-mutated cells. HDAC2 interacts with EZH2 in an ARID1A status-dependent manner. HDAC2 functions as a co-repressor of EZH2 to suppress the expression of EZH2/ARID1A target tumor suppressor genes such as PIK3IP1 to inhibit proliferation and promote apoptosis. SAHA reduced the growth and ascites of the ARID1A-inactivated OCCCs in both orthotopic and genetic mouse models. This correlated with a significant improvement of survival of mice bearing ARID1A-mutated OCCCs. These findings provided preclinical rationales for repurposing FDA-approved pan-HDAC inhibitors for treating ARID1A-mutated cancers. Fukumoto et al. show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers. This correlated with enhanced growth suppression induced by the inhibition of HDAC2 activity in ARID1A-mutated cells. These findings provided preclinical rationales for repurposing FDA-approved pan-HDAC inhibitors for treating ARID1A-mutated cancers.
dc.subject ARID1A
dc.subject chromatin remodeling
dc.subject HDAC2
dc.subject ovarian cancer
dc.subject pan-HDAC inhibitor
dc.subject SAHA
dc.subject SWI/SNF
dc.title Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer
dc.type Article
dc.relation.ispartofseries-issue 13
dc.relation.ispartofseries-volume 22
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 3393
dc.source.id SCOPUS-2018-22-13-SID85043984145


Files in this item

This item appears in the following Collection(s)

  • Публикации сотрудников КФУ Scopus [22633]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

Show simple item record

Search DSpace


Advanced Search

Browse

My Account