Crosstalk Between Caveolin 1 And Cholesterol Biosynthesis in Regulating Glioblastoma Stem Cells Population

Abstract

Glioblastoma, one of the most aggressive brain tumors, has survival rate of 12- 16 moths. Cancer stem cells are root cause of cancer recurrence and drug resistance. Due to blood brain barrier the peripheral cholesterol is not accessible by the brain and the astrocytes need to perform de novo cholesterol biosynthesis which maintains a separate cholesterol pool. High cholesterol is associated with various cancer progression and it also fuels the stem cell maintenance. As, cholesterol and Caveolin-1 regulate each other, through this study the effect of cholesterol biosynthesis inhibition on glioma stem cell proliferation is elucidated. Cholesterol biosynthesis inhibition by lovastatin reduces stemness through downregulation of Caveolin-1. Downregulation of Caveolin-1 is due to the epigenetic repressor KDM5A, which demethylates H3K4me3 mark from Caveolin-1 promoter. Cholesterol downregulation hampers hedgehog signaling and affects the expression of KDM5A. So, both cholesterol and Caveoli-1 are essential for glioma stem cell maintenance and targeting Caveolin-1 and cholesterol can have therapeutic importance.