Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m 6 A-demethylation of NANOG mRNA
Johns Hopkins University · Sun Yat-sen University · +3 more institutions
Abstract
N(6)-methyladenosine (m(6)A) modification of mRNA plays a role in regulating embryonic stem cell pluripotency. However, the physiological signals that determine the balance between methylation and demethylation have not been described, nor have studies addressed the role of m(6)A in cancer stem cells. We report that exposure of breast cancer cells to hypoxia stimulated hypoxia-inducible factor (HIF)-1α- and HIF-2α-dependent expression of AlkB homolog 5 (ALKBH5), an m(6)A demethylase, which demethylated NANOG mRNA, which encodes a pluripotency factor, at an m(6)A residue in the 3'-UTR. Increased NANOG mRNA and protein expression, and the breast cancer stem cell (BCSC) phenotype, were induced by hypoxia in an…
Citation impact
- FWCI
- 40.21
- Percentile
- 100%
- References
- 48
Authors
8- CZChuanzhao Zhang
Johns Hopkins University, Sun Yat-sen University, Johns Hopkins Medicine, The First Affiliated Hospital, Sun Yat-sen University
- DSDebangshu Samanta
Johns Hopkins University, Johns Hopkins Medicine
- HLHaiquan Lu
Johns Hopkins University, Johns Hopkins Medicine
- JWJohn W. Bullen
Johns Hopkins University, Johns Hopkins Medicine
- HZHuimin Zhang
University of Minnesota, Johns Hopkins University, Johns Hopkins Medicine
Topics & keywords
- Homeobox protein NANOG
- Cancer research
- Biology
- Cancer stem cell
- Nanog Homeobox Protein
- Stem cell
- HIF1A
- Metastasis
- Good health and well-being