Article ; Online: Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer.
2016 Volume 7, Issue 52, Page(s) 86816–86828
Abstract: ... mice. Taken together, colon CSCs overexpress Prdx2, which promotes their stem cell properties via ... Redox status is a critical factor in the maintenance of CSCs, and the antioxidant enzyme Peroxiredoxin 2 ... signaling pathway. Finally, knockdown of Prdx2 in CD133+ cells reduced the volume of xenograft tumors in BALB/c-nu ...
| 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. |
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| MeSH term(s) | Animals ; Antimetabolites, Antineoplastic/pharmacology ; Apoptosis/drug effects ; Apoptosis/genetics ; Cell Line, Tumor ; Cell Self Renewal/drug effects ; Colonic Neoplasms/genetics ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/therapy ; Female ; Fluorouracil/pharmacology ; HCT116 Cells ; HT29 Cells ; Hedgehog Proteins/metabolism ; Humans ; Mice, Inbred BALB C ; Mice, Nude ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Peroxiredoxins/genetics ; Peroxiredoxins/metabolism ; Phenotype ; RNA Interference ; RNAi Therapeutics/methods ; Signal Transduction ; Spheroids, Cellular/drug effects ; Spheroids, Cellular/metabolism ; Xenograft Model Antitumor Assays/methods |
| Chemical Substances | Antimetabolites, Antineoplastic ; Hedgehog Proteins ; Peroxiredoxins (EC 1.11.1.15) ; Fluorouracil (U3P01618RT) |
| Language | English |
| Publishing date | 2016-11-23 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2560162-3 |
| ISSN | 1949-2553 ; 1949-2553 |
| ISSN (online) | 1949-2553 |
| ISSN | 1949-2553 |
| DOI | 10.18632/oncotarget.13559 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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