EPISODE · Sep 1, 2026 · 21 MIN
1522-PIKfyve-ER应激轴定义神经内分泌前列腺癌代谢脆弱性
from 聊聊Sci
该研究揭示了神经内分泌前列腺癌（NEPC）在极端微环境下的生存机制，并发现PIKfyve脂质激酶是其应对代谢压力的核心节点。NEPC肿瘤普遍存在高水平的内质网应激（ER stress），而PIKfyve通过维持溶酶体功能和脂质回收来抵消这种压力，促进肿瘤存活。当抑制PIKfyve时，癌细胞会启动由SREBP驱动的代偿性脂质合成程序，以维持膜稳态并逃避凋亡。研究进一步证明，联合抑制PIKfyve与脂肪酸合成酶（FASN）可阻断这一适应性通路，引发终末未折叠蛋白反应。这种双重靶向策略在临床前模型中展现出显著的协同杀伤作用，为治疗这种极具侵略性的癌症亚型提供了全新的代谢脆弱性靶点。References:Zheng Y, Cheng C, Cao Y, et al. A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer[J]. Cancer Cell, 2026.前往小宇宙评论区与主播互动
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1522-PIKfyve-ER应激轴定义神经内分泌前列腺癌代谢脆弱性
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