title: Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer.
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.
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jinlai
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Shouru
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xingye
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jinbao
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Maoxi
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Kunli
authors.initials: K
authors.lastname: Du
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Linglong
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhenbing
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Wenxian
authors.initials: W
authors.lastname: You
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhongxue
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D045325:HCT116 Cells; D019073:HT29 Cells; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000964:Antimetabolites, Antineoplastic; D053823:Hedgehog Proteins; D054464:Peroxiredoxins; D005472:Fluorouracil
keywords: Hedgehog; Prdx2; cancer stem cell; colon cancer; stemness