Cellular and Molecular Mechanisms of Plasticity of Glioblastoma Stem Cells

Glioblastoma (GBM) is one of the most malignant and common human brain tumors. This tumor contains glioblastoma stem cells (GSCs), which drive tumor growth, progression, and metastasis even after surgical resection, radiation, and chemotherapy. Physiological changes within the body facilitate the adaptation, maintenance, survival, and proliferation of GBM cells. Underlying this cellular plasticity is the asymmetric division of GBM cells, which gives rise to diverse cancer cell types. Consequently, the issue of GBM plasticity is crucial for understanding tumor biology and developing effective therapeutic strategies. This review focuses on GBM heterogeneity, associated markers, microRNAs, long non-coding RNAs, signaling cascades (kinases, transcription factors), genes, and transitions between distinct cellular phenotypes. It examines the expression and regulation of GSC markers across various cellular states are influenced by cell cycle phases and the transition from a proneural (PN) to a mesenchymal phenotype (MES)— proneural-mesenchymal transition (PMT) which are associated with changes in cellular activity. The PN and MES of GBM cells are represented as a dynamic continuum of transitional states underlying the processes of self-renewal, proliferation, invasion migration, therapy resistance, and differentiation. Further research is needed to elucidate the molecular mechanisms of GBM cellular plasticity involved in angiogenesis, metastasis, and immunosuppression of the tumor microenvironment.