AP-1 confers resistance to anti-cancer therapy by activating XIAP

The underlying cause of treatment failure in many cancer patients is intrinsic and acquired resistance to chemotherapy. Recently, histone deacetylase (HDAC) inhibitors have developed into a promising cancer treatment. However, resistance mechanism induced by HDAC inhibitors remains largely unknown....

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Published in:Oncotarget 2018-03, Vol.9 (18), p.14124-14137
Main Authors: Wang, Yuan, Wan, Guo-Hui, Wu, Ying-Min, Wang, Hong-Sheng, Wang, Hai-Fang, Zhang, Ge, Lu, Lin-Lin, Li, Zi-Qian, Chan, Ka-Ying, Zhou, Yan, Cai, Shao-Hui, Qi, Yi-Fei, Du, Jun
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Language:English
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Research Paper
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Summary:The underlying cause of treatment failure in many cancer patients is intrinsic and acquired resistance to chemotherapy. Recently, histone deacetylase (HDAC) inhibitors have developed into a promising cancer treatment. However, resistance mechanism induced by HDAC inhibitors remains largely unknown. Here we report that a HDAC inhibitor, JNJ-2648158 induced transcription of XIAP by activating AP-1 expression, which conferring resistance to chemotherapeutics. Our results showed that high expression of c-Fos caused by HDAC inhibitor promoted AP-1 formation during acquired resistance towards chemo-drugs, indicating an extremely poor clinical outcome in breast cancers and liver cancers. Our study reveals a novel regulatory mechanism towards chemo-drug resistance, and suggests that XIAP may serve as a potential therapeutic target in those chemo-resistant cancer cells.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.23897