Temozolomide promotes glioblastoma stemness expression through senescence-associated reprogramming via HIF1α/HIF2α regulation.

ABSTRACT: A critical challenge in glioblastoma multiforme (GBM) treatment is that tumors recurring after temozolomide (TMZ) therapy become more malignant, exhibiting increased invasiveness and stemness compared to the primary tumor. However, the underlying mechanisms remain unclear. While the majority of GBM cells are eradicated by TMZ, a subset enters cell cycle arrest, adopts a senescence-associated secretory phenotype (SASP), and activates senescence-related signaling pathways. These cells eventually escape senescence, re-enter the cell cycle, and form aggregates exhibiting stem-like characteristics such as elevated stemness marker expression, enhanced colony formation, increased invasiveness, and resistance to chemotherapy. Furthermore, these aggregates promote the invasion and chemotherapy resi

SUBMITTER: Wang P 

PROVIDER: S-EPMC12009364 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature