胆固醇是细胞膜的重要结构成分，而过量的胆固醇可能有毒，因此会储存在细胞内脂滴 (LD) 中。恶性肿瘤细胞生长迅速，需要丰富的胆固醇来构建新的细胞膜。它们如何维持胆固醇稳态尚不清楚。我们最近发现，SREBF1/SREBP-1（甾醇调节元件结合转录因子 1）是一种关键的脂肪生成转录因子，在维持肿瘤细胞中胆固醇稳态方面发挥着关键作用。我们发现，除了激活脂质从头合成和胆固醇摄取外，SREBF1还上调巨自噬/自噬水解LD，并增加溶酶体胆固醇转运蛋白NPC2的表达，主动动员LD储存的胆固醇和脂肪酸促进肿瘤发生生长。我们的研究表明，SREBF1 控制脂质合成、摄取、储存和释放的平衡，以维持脂质稳态以促进肿瘤的快速生长，同时表明它是一个非常有前途的癌症治疗分子靶点。

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.