Qki deficiency maintains sternness of glioma stem cells in suboptimal environment by downregulating endolysosomal degradation

Stem cells, including cancer stem cells (CSCs), require niches to maintain sternness, yet it is unclear how CSCs maintain sternness in the suboptimal environment outside their niches during invasion. Postnatal co-deletion of Pten and Trp53 in mouse neural stem cells (NSCs) leads to the expansion of these cells in their subventricular zone (SVZ) niches but fails to maintain sternness outside the SVZ. We discovered that Qki is a major regulator of NSC sternness. Qk deletion on a Pten(-/-); Trp53(-/-) background helps NSCs maintain their sternness outside the SVZ in Nes-CreER(T2); QkL/L; ptenuL; Trp53(L/L) mice, which develop glioblastoma with a penetrance of 92% and a median survival time of 105 d. Mechanistically, Qk deletion decreases endolysosome-mediated degradation and enriches receptors essential for maintaining self-renewal on the cytoplasmic membrane to cope with low ligand levels outside niches. Thus, downregulation of endolysosome levels by Qki loss helps glioma stem cells (GSCs) maintain their sternness in suboptimal environments outside their niches.