{"title":"Glycoconjugated Metallohelices Eliminate Cancer Stem-Like Cells via Modulating G-Quadruplex Surrounding Transcriptional Start Site of Sox2 Gene.","authors":"Hongshuang Qin,Jie Yang,Tingting Cui,Hualong Song,Miles Postings,Peter Scott,Chunyu Wang,Chuanqi Zhao,Jinsong Ren,Xiaogang Qu","doi":"10.1002/anie.202503488","DOIUrl":null,"url":null,"abstract":"As an important pluripotency transcription factor, Sox2 plays key roles in the stemness maintenance of cancer stem-like cells (CSCs). Here, we found that a highly conserved G-rich region surrounding transcriptional start sites (TSSs) of Sox2 gene can form G-quadruplex (Sox2G4) both in vitro and in cells. More intriguingly, the glycoconjugated triplex metallohelice [Fe2LΔ-f 3]4+ (Δ-f) can enantioselectively stabilize Sox2G4. Sox2G4 stabilization induced by [Fe2LΔ-f 3]4+ (Δ-f) rather than Λ-f results in inhibition of Sox2 expression both in mRNA and protein levels in breast CSCs and decreases the cell viability and stemness of breast CSCs. These results indicate that [Fe2LΔ-f 3]4+ (Δ-f) has the enantioselectivity even in living cells. In vivo studies further demonstrate that Δ-f can reduce tumor initiation of breast CSCs. To our knowledge, this is the first report that targeting G-quadruplexes of pluripotency genes can regulate the fates of CSCs. Our work provides a new way to target CSC gene and eradicate cancer stem cells.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"19 1","pages":"e202503488"},"PeriodicalIF":16.9000,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angewandte Chemie International Edition","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1002/anie.202503488","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
As an important pluripotency transcription factor, Sox2 plays key roles in the stemness maintenance of cancer stem-like cells (CSCs). Here, we found that a highly conserved G-rich region surrounding transcriptional start sites (TSSs) of Sox2 gene can form G-quadruplex (Sox2G4) both in vitro and in cells. More intriguingly, the glycoconjugated triplex metallohelice [Fe2LΔ-f 3]4+ (Δ-f) can enantioselectively stabilize Sox2G4. Sox2G4 stabilization induced by [Fe2LΔ-f 3]4+ (Δ-f) rather than Λ-f results in inhibition of Sox2 expression both in mRNA and protein levels in breast CSCs and decreases the cell viability and stemness of breast CSCs. These results indicate that [Fe2LΔ-f 3]4+ (Δ-f) has the enantioselectivity even in living cells. In vivo studies further demonstrate that Δ-f can reduce tumor initiation of breast CSCs. To our knowledge, this is the first report that targeting G-quadruplexes of pluripotency genes can regulate the fates of CSCs. Our work provides a new way to target CSC gene and eradicate cancer stem cells.
期刊介绍:
Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.