Abstract:
:BET inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. However, the identification of new potential targets to enhance breast cancer sensitivity to BETi is still an enormous challenge. Both NR5A2 and NCOA3 are frequently involved in cancer cells resistance to chemotherapy, also associated with poor prognosis in breast cancer. However, the functions of NR5A2 and NCOA3 in BETi resistance remains unknown. In this study, we found that BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, we identified NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes. Moreover, inhibition of NR5A2 or NCOA3 using small molecule inhibitors enhanced anti-cancer effects of BETi against breast cancer in vivo and in vitro. Altogether, our findings illustrated NR5A2 synergized with NCOA3 to confer breast cancer cells resistance to BETi by induction of NRF2. Inhibition of NR5A2/NCOA3 combined with BETi might be a novel strategy for treatment of breast cancer.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Qiao J,Chen Y,Mi Y,Jin H,Huang T,Liu L,Gong L,Wang L,Wang Q,Zou Zdoi
10.1016/j.bbrc.2020.05.069subject
Has Abstractpub_date
2020-09-17 00:00:00pages
402-409issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(20)30977-3journal_volume
530pub_type
杂志文章abstract::Recent reports have shown that the endoplasmic reticulum (ER) stress is relevant to the pathogenesis of Alzheimer disease. Following the amyloid cascade hypothesis, we therefore attempted to investigate the effects of ER stress on amyloid-beta peptide (Abeta) generation. In this study, we found that ER stress altered ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2006.03.173
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2017.06.033
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(91)91885-g
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2012.05.162
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1993.1213
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2012.10.097
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2003.11.146
更新日期:2004-01-16 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(89)92261-4
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1998.8806
更新日期:1998-07-09 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1998.9038
更新日期:1998-07-30 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(84)90754-x
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1994.2121
更新日期:1994-08-15 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2002.6491
更新日期:2002-03-08 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(84)90383-8
更新日期:1984-08-30 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2005.05.090
更新日期:2005-07-22 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2010.08.058
更新日期:2010-09-24 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2001.5764
更新日期:2001-10-19 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1998.9992
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
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更新日期:2004-09-17 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
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更新日期:2011-12-02 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1995.1052
更新日期:1995-01-05 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1996.0148
更新日期:1996-01-26 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
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更新日期:2008-11-07 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1993.1639
更新日期:1993-05-28 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2002.6583
更新日期:2002-03-15 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
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更新日期:2012-10-12 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
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更新日期:2006-11-24 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1994.2395
更新日期:1994-09-30 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2008.06.084
更新日期:2008-09-05 00:00:00
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2000.3255
更新日期:2000-08-18 00:00:00