Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

摘要: Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, top differentially expressed gene compared tissue-specific progenitors. Direct interrogation uptake demonstrated that potently extract from microenvironment more effectively than other tumor cells. Systematic flux determined preferentially require transferrin receptor ferritin, two core regulators, propagate form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through STAT3-FoxM1 axis, revealing an iron-regulated pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which have epigenetically programmed, targetable dependence.