Oncotarget

Research Papers:

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

Yuan Wang _, Guo-Hui Wan, Ying-Min Wu, Hong-Sheng Wang, Hai-Fang Wang, Ge Zhang, Lin-Lin Lu, Zi-Qian Li, Ka-Ying Chan, Yan Zhou, Shao-Hui Cai, Yi- Fei Qi and Jun Du

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Oncotarget. 2018; 9:14124-14137. https://doi.org/10.18632/oncotarget.23897

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Abstract

Yuan Wang1, Guo-Hui Wan1, Ying-Min Wu1, Hong-Sheng Wang1, Hai-Fang Wang1, Ge Zhang1, Lin-Lin Lu1, Zi-Qian Li1, Ka-Ying Chan1, Yan Zhou1, Shao-Hui Cai2, Yi-Fei Qi1 and Jun Du1

1Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China

2Department of Pharmacology, School of Pharmaceutical Sciences, Jinan University, Guangzhou 510632, China

Correspondence to:

Jun Du, email: [email protected]

Keywords: drug resistant; HDAC inhibitor; JNJ26481585; AP-1; XIAP

Received: June 21, 2017     Accepted: October 30, 2017     Epub: January 03, 2018     Published: March 06, 2018

ABSTRACT

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.


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