Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer

// Rong Wang 1 , Jinlai Wei 1 , Shouru Zhang 1 , Xingye Wu 1 , Jinbao Guo 1 , Maoxi Liu 1 , Kunli Du 1 , Jun Xu 1 , Linglong Peng 1 , Zhenbing Lv 1 , Wenxian You 1 , Yongfu Xiong 1 , Zhongxue Fu 1 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China Correspondence to: Zhongxue Fu, email: fzx19990521@126.com Keywords: Prdx2, stemness, cancer stem cell, Hedgehog, colon cancer Received: August 10, 2016      Accepted: November 11, 2016      Published: November 24, 2016 ABSTRACT Cancer stem cells (CSCs) are a key target for reducing tumor growth, metastasis, and recurrence. Redox status is a critical factor in the maintenance of CSCs, and the antioxidant enzyme Peroxiredoxin 2 (Prdx2) plays an important role in the development of colon cancer. Therefore, we investigated the contribution of Prdx2 to the maintenance of stemness of colon CSCs. Here, we used short-hairpin RNAs and a Prdx2-overexpression vector to determine the effects of Prdx2. We demonstrated that knockdown of Prdx2 reduced the self-renewal and sphere formation and resulted in increased 5-FU-induced apoptosis in human colon CSCs. Prdx2 overexpression induced reversion of the self-renewal and sphere formation. Furthermore, the effects of Prdx2 resulted in an altered expression of stemness associated with the Hh/Gli1 signaling pathway. Finally, knockdown of Prdx2 in CD133 + cells reduced the volume of xenograft tumors in BALB/c-nu mice. Taken together, colon CSCs overexpress Prdx2, which promotes their stem cell properties via the Hh/Gli1 signaling pathway. The results suggest that Prdx2 may be an effective therapeutic target for the elimination of CSCs in colorectal cancer.