Tumor Cell "Slimming" Regulates Tumor Progression through PLCL1/UCP1-Mediated Lipid Browning
Tumor Cell "Slimming" Regulates Tumor Progression through PLCL1/UCP1-Mediated Lipid Browning
复制标题
肿瘤细胞“瘦身”通过 PLCL1/UCP1 介导的脂质褐变调节肿瘤进展
DOI：
10.1002/advs.201801862
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发表时间：
2019-05-17
期刊：
影响因子：
15.1
通讯作者：
Zhang, Xiaoping
中科院分区：
文献类型：
--
作者：
Xiong, Zhiyong;Xiao, Wen;Zhang, Xiaoping
新的证据强调了异常脂质积累在癌症发生和进展中的重要作用，但这种现象的机制仍不清楚。在此，研究证明磷脂酶 C 样 1/解偶联蛋白 1 (PLCL1)/(UCP1) 介导的脂质褐变可促进肿瘤细胞“瘦身”并抑制肿瘤进展。通过筛选透明细胞肾细胞癌（ccRCC）中三个独立的脂质代谢相关基因集并分析TCGA数据库，发现PLCL1预测不良预后并在ccRCC中下调。 ccRCC 细胞中 PLCL1 表达的恢复可显着抑制肿瘤进展并减少异常脂质积累。此外，还观察到一种称为肿瘤细胞“瘦身”的现象，即肿瘤细胞体积缩小，脂滴转变为微小碎片。进一步的研究表明，PLCL1 通过 UCP1 介导的脂质褐变（消耗脂质而不产生 ATP 能量）来促进肿瘤细胞“瘦身”并抑制肿瘤进展。机理研究表明 PLCL1 通过影响蛋白质泛素化水平来提高 UCP1 的蛋白质稳定性。总的来说，数据表明 PLCL1/UCP1 介导的脂质褐变促进肿瘤细胞“瘦身”并消耗异常的脂质积累，从而抑制 ccRCC 的进展。肿瘤细胞“瘦身”为对抗肿瘤的发生和进展提供了一种有前景的新概念和治疗方式。
Emerging evidence has highlighted the important role of abnormal lipid accumulation in cancer development and progression, but the mechanism for this phenomenon remains unclear. Here, it is demonstrated that phospholipase C-like 1/uncoupling protein 1 (PLCL1)/(UCP1)-mediated lipid browning promotes tumor cell "slimming" and represses tumor progression. By screening three independent lipid metabolism-related gene sets in clear cell renal cell carcinoma (ccRCC) and analyzing the TCGA database, it is found that PLCL1 predicted a poor prognosis and was downregulated in ccRCC. Restoration of PLCL1 expression in ccRCC cells significantly represses tumor progression and reduces abnormal lipid accumulation. Additionally, a phenomenon called tumor cell "slimming," in which tumor cell volume is reduced and lipid droplets are transformed into tiny pieces, is observed. Further studies show that PLCL1 promotes tumor cell "slimming" and represses tumor progression through UCP1-mediated lipid browning, which consumes lipids without producing ATP energy. Mechanistic investigations demonstrate that PLCL1 improves the protein stability of UCP1 by influencing the level of protein ubiquitination. Collectively, the data indicate that lipid browning mediated by PLCL1/UCP1 promotes tumor cell "slimming" and consumes abnormal lipid accumulation, which represses the progression of ccRCC. Tumor cell "slimming" offers a promising new concept and treatment modality against tumor development and progression.