OSBPL2-mediated lipid metabolism alteration governs lung cancer stem cells properties

Lung cancer is the first leading cause of cancer death worldwide. oxysterol-binding protein-like 2 (OSBPL2), is a lipid transport protein regulating cholesterol homeostasis. Here, we clarified the previously unreported role of OSBPL2 in lung cancer stemness properties. We observed that OSBPL2 reduced cholesterol content by HPLC-MS. It inhibited the accumulation of lipid droplets (LDs) in lung cancer. OSBPL2-mediated lipid transportation significantly suppressed tumor sphere formation, stemness markers expression and in vivo tumorigenesis and tumor metastasis. In clinical specimens, we also demonstrated that OSBPL2 repressed the expression of Lung cancer stem-like cells (LCSCs) markers-ALDH1A1, CD133 and Nanog. The level of OSBPL2 was negatively correlated with malignant of lung cancer, such as tumor stage progression and lymph node metastasis. Taken together, these findings illustrated that OSBPL2-mediated lipid transportation inhibited the stemness and aggressiveness of lung cancer cells. OSBPL2 was a potential therapeutic target to develop novel cancer-preventive compound.