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/

Zendy Plus

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

Zendy Tools

Zendy Open

Alterations in genes coding for histone modifiers are found in human cancers, suggesting that histone modification is involved in malignant features of neoplastic cells. This study showed that a histone demethylase KDM4C is significant for colonosphere formation by mediating the cross talk between oncogenic pathways through a feed-forward mechanism. The expression ofKDM4Cgene was increased in spheres from colorectal cancer (CRC) cells and the knockdown (KD) of KDM4C eliminated colonosphere formation. We found that the KD of β-catenin, an important oncogenic factor in CRC, resulted in not only decreased sphere formation but also impaired upregulation ofKDM4Cgene in spheres. β-Catenin bound to theKDM4Cpromoter, suggesting that KDM4C is involved in the sphere-forming ability downstream of β-catenin in CRC cells. Microarray analysis identified theJAG1gene that codes for a notch ligand Jagged1 responsible for sphere formation as a target of KDM4C.KDM4CKD decreased the expression ofJAG1gene, and the downregulation ofJAG1gene recapitulated the impaired colonosphere formation.JAG1is also a target of β-catenin, and chromatin immunoprecipitation analysis showed the binding of β-catenin and KDM4C onto theJAG1promoter during colonosphere formation. Importantly,KDM4CKD ruined the recruitment of β-catenin onto theJAG1promoter independently of the H3-K9 methylation status and bluntedJAG1expression during sphere formation. These data indicate that KDM4C maintains the sphere-forming capacity in CRCs by mediating the β-catenin-dependent transcription ofJAG1in a feed-forward manner.

Histone demethylase KDM4C regulates sphere formation by mediating the cross talk between Wnt and Notch pathways in colonic cancer cells