HMGA2 enhances 5-fluorouracil chemoresistance in colorectal cancer via the Dvl2/Wnt pathway

// Xi Xu 1, 2 , Yunfeng Wang 3 , Hong Deng 1, 2 , Chungang Liu 1, 2, 4 , Jingjing Wu 1, 2 and Maode Lai 1, 2 1 Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China 2 Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China 3 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, 150081, China 4 Center of Biological Therapy, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China Correspondence to: Maode Lai, email: lmp@zju.edu.cn Jingjing Wu, email: wujingjing@zju.edu.cn Keywords: HMGA2; Dvl2; 5-FU; chemoresistance; colorectal cancer Received: July 12, 2017      Accepted: December 03, 2017      Published: January 10, 2018 ABSTRACT Drug resistance is one of the main hurdles to overcome for the improvement of cancer patient survival. However, the underlying mechanisms remain largely unknown, and therapeutic options are limited. Here, we demonstrate a strong correlation between HMGA2 expression and chemosensitivity to 5-fluorouracil (5-FU), a widely used first-line systemic chemotherapy regimen for colorectal cancer (CRC) patients. Overexpression of HMGA2 enhances chemoresistance to 5-FU of CRC both in vitro and in vivo . Further experiments indicate that HMGA2 directly binds to the promoter of Dvl2 and induces its transcription, which leads to increased activation of the Wnt/β-catenin pathway. Taken together, our data suggest that HMGA2 enhances the chemoresistance to 5-FU in CRC via activating the Dvl2/Wnt pathway. Therefore, HMGA2 may serve as a predictive biomarker and a potential therapeutic target in CRC.