甾醇调节元件结合蛋白
生物
胆固醇
甾醇
脂质代谢
脂滴
平衡
转录因子
自噬
细胞生物学
生物化学
细胞凋亡
基因
出处
期刊:Autophagy
[Informa]
日期:2023-11-05
卷期号:: 1-3
标识
DOI:10.1080/15548627.2023.2275501
摘要
Cholesterol is an essential structural component of the cell membrane, whereas excess cholesterol can be toxic and thus is stored in intracellular lipid droplets (LDs). Malignant tumor cells grow rapidly and require abundant cholesterol to build new membranes. How they maintain cholesterol homeostasis is largely unknown. We recently revealed that SREBF1/SREBP-1 (sterol regulatory element binding transcription factor 1), a key lipogenic transcription factor, plays a critical role in maintaining cholesterol homeostasis in tumor cells. We found that in addition to activation of de novo lipid synthesis and cholesterol uptake, SREBF1 also upregulates macroautophagy/autophagy to hydrolyze LDs, and increases the expression of NPC2, a lysosome cholesterol transporter, actively mobilizing LD-stored cholesterol and fatty acids to promote tumor growth. Our study demonstrates that SREBF1 controls the balance of lipid synthesis, uptake, storage and liberation to maintain lipid homeostasis for rapid tumor growth, while suggesting it as a very promising molecular target for cancer treatment.
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