Morphofunctional Heterogeneity and Plasticity of Glioblastoma Cells Induced to Senescence by Temozolomide - PubMed
8 hours ago
- #phenotypic plasticity
- #cellular senescence
- #glioblastoma
- Temozolomide (TMZ) induces senescence in glioblastoma cells, leading to two distinct morphotypes: extension-rich (E-state) cells and flattened (F-state) cells, which are interchangeable, primarily from E-state to F-state.
- F-state cells show progressive enlargement in cellular and nuclear area, lower levels of p16 and autophagy, and reduced anti-apoptotic Bcl-2 proteins compared to E-state cells, suggesting a more stable senescent phenotype.
- Autophagy inhibition timing affects cell states: late inhibition with hydroxychloroquine sensitizes both morphotypes, while early inhibition with 3-methyladenine promotes E-state accumulation.
- Senolytic drugs like dasatinib preferentially eliminate E-state cells, highlighting the need for targeted senotherapeutic strategies to address the heterogeneity and plasticity of senescent cancer cells.