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