English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Cancer stem cells (CSCs) have tumour initiation, self-renewal, and long-term tumour repopulation properties, and it is postulated that differentiated somatic cells can be reprogrammed to CSCs by oncogenic signals. We previously showed that oncogenic  HRAS   V12   conferred tumour initiation capacity in tumour suppressor p53-deficient ( p53   −/−  ) primary mouse embryonic fibroblasts (MEFs) through transcription factor NF-κB-mediated enhancement of glucose uptake; however, the underlying mechanisms of  RAS  oncogene-induced CSC reprogramming have not been elucidated. Here, we found that the expression of the reprogramming factor  SOX2  was induced by  HRAS   V12   in  p53   −/−   MEFs. Moreover, gene knockout studies revealed that  SOX2  is an essential factor for the generation of CSCs by  HRAS   V12   in mouse and human fibroblasts. We demonstrated that HRAS V12 -induced cyclin-dependent kinase 1 (CDK1) activity and subsequent enhancement of protein  O -GlcNAcylation were required for SOX2 induction and CSC generation in these fibroblasts and cancer cell lines containing  RAS  mutations. Moreover, the CDK inhibitor dinaciclib and  O -GlcNAcylation inhibitor OSMI1 reduced the number of CSCs derived from these cells. Taken together, our results reveal a signalling pathway and mechanism for CSC generation by oncogenic  RAS  and suggest the possibility that this signalling pathway is a therapeutic target for CSCs.

Enhanced O-GlcNAc modification induced by the RAS/MAPK/CDK1 pathway is required for SOX2 protein expression and generation of cancer stem cells