Back to Search
Start Over
Inherited KDM6AA649Tfacilitates tumor-immune escape and exacerbates colorectal signet-ring cell carcinoma outcomes
- Source :
- Oncogene; 20240101, Issue: Preprints p1-12, 12p
- Publication Year :
- 2024
-
Abstract
- Childhood onset of colorectal signet-ring cell carcinoma (CR-SRCC) is extremely rare and featured as highly malignant with poor prognosis. Here we reported a CR-SRCC case of 11-year-old boy with a novel inherited X-linked KDM6AA694Tmutation. The H3K27me3 demethylase KDM6A was frequently mutated in varieties of tumors and acts as a tumor suppressor. In vivo H3K27me3 demethylation assay demonstrated that KDM6AA694Thad dampened H3K27me3 demethylase activity. Overexpression of KDM6AA694Tin SRCC cell line KATO3 promoted cell proliferation, invasion and migration, which were further confirmed in vivo by constructing orthotopic tumor growth and lung metastasis model. Besides, expression of KDM6AA694Tin immune cells suppresses inflammatory macrophage response and effector T cell response. In conclusion, we characterized a novel inherited KDM6AA694Tmutant from a childhood-onset SRCC case and demonstrated that the mutant with impaired H3K27me3 demethylase activity could potentiate tumor malignancy and suppress antitumor immunity.
Details
- Language :
- English
- ISSN :
- 09509232 and 14765594
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Oncogene
- Publication Type :
- Periodical
- Accession number :
- ejs66087142
- Full Text :
- https://doi.org/10.1038/s41388-024-03029-w