Back to Search
Start Over
AMPK-mediated CD47 H3K4 methylation promotes phagocytosis evasion of glioma stem cells post-radiotherapy.
- Source :
-
Cancer Letters . Feb2024, Vol. 583, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
-
Abstract
- Radiotherapy alters the tumor microenvironment and reprograms cellular metabolism. Transition of tumor cell phenotypes contributes to post-radiotherapy tumor recurrence. Low radiosensitivity of glioma stem cells is one of the reasons for radiotherapy failure. Here, we found that radiotherapy resulted in a higher proportion of infiltration of inflammatory macrophages in glioma non-stem cell grafts compared with that in glioma stem cell-transplanted tumors in a mouse model, where immunosuppressive macrophages dominated in the tumor microenvironment. In radioresistant glioma stem cells, ionizing radiation upregulated CD47 expression by AMP-activated protein kinase (AMPK), resulting in the inhibition of phagocytosis and the promotion of M2-like polarization in macrophages. Ionizing radiation promoted H3K4 methylation on CD47 promotor by downregulating KDM5A. Hyper-phosphorylated retinoblastoma protein RB maintained its dissociation status with KDM5A following AMPK activation, which inhibited the demethylated function of KDM5A. In contrast, in radiosensitive glioma non-stem cells, RB S807/S811 hypo-phosphorylation contributed to the binding of RB with KDM5A, which suppressed H3K4 methylation on CD47 promotor. In addition, ionizing radiation promoted H3K27 acetylation on CD47 promotor by HDAC7 in glioma stem cells. These data suggested that glioma stem cells reprogrammed the tumor immune microenvironment by epigenetic editing to escape macrophage phagocytosis after ionizing radiation. Targeting CD47 might be a potential strategy to sensitize glioblastoma to radiotherapy. • RB S807/S811 phosphorylation is important for the binding of RB with KDM5A in radiosensitive glioma non-stem cells. • RB maintains in a hyper-phosphorylated status in radioresistant glioma stem cells after radiation. • The dissociation of hyper-phosphorylated RB with KDM5A induces H3K4 methylation on CD47 promotor. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 583
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 175190670
- Full Text :
- https://doi.org/10.1016/j.canlet.2023.216605