Fig. 2.1.
Hypoxia-Activated Pathways Leading to Cancer Stem Cell Maintenance. Multiple stem cell-related genes encoding cell surface proteins, transcription factors, or chromatin modifying enzymes are up-regulated under hypoxic conditions either directly by the HIF transcription factor pathway or by other yet unknown mechanisms. These different pathways may function either synergistically or additively to maintain cancer stem cells by enhancing their self-renewal and blocking their differentiation. Increased lifespan of cancer stem cells allows inheritable accumulation of multiple genetic mutations and epigenetic changes that are crucial for clonal evolution and malignant progression.