C/EBPδ-Slug-Lox1 axis promotes metastasis of lung adenocarcinoma via oxLDL uptake
C/EBPδ-Slug-Lox1 axis promotes metastasis of lung adenocarcinoma via oxLDL uptake
复制标题
C/EBP delta-Slug-Lox1轴通过oxLDL摄取促进肺腺癌转移
DOI：
10.1038/s41388-019-1015-z
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发表时间：
2020-01-01
期刊：
影响因子：
8
通讯作者：
Xu, Lingyan
中科院分区：
文献类型：
--
作者：
Wang, Dongmei;Cheng, Xinghua;Xu, Lingyan
癌细胞经历重要的脂质代谢重编程，以确保足够的能量供应以维持生存和发展。然而，癌细胞如何将脂质代谢信号与癌症进展相结合尚不清楚。在本研究中，我们证明了C/EBP δ，一个关键的脂质代谢调节因子，是tgf - β 1下游基因，促进肺腺癌转移。重要的是，C/EBP δ在脂质代谢和上皮到间质转化（EMT）基因网络中引起了显著的振荡。在机制上，我们证明了C/EBP δ募集癌基因NCOA3转录激活Slug，这是一种典型的EMT转录因子，反过来诱导oxLDL受体-1 （Lox1）表达并增强oxLDL摄取以促进癌症转移，这可以被Lox1中和抗体阻断。总之，我们的研究结果揭示了脂质代谢和转移程序之间的相互作用，以及关键的C/EBP delta-Slug-Lox1转录轴的存在，以促进oxLDL水平和癌症转移。
Cancer cells undergo significant lipid metabolic reprogramming to ensure sufficient energy supply for survival and progression. However, how cancer cells integrate lipid metabolic signaling with cancer progression is not well understood. In the present study, we demonstrated that C/EBP delta, a critical lipid metabolic regulator, is a TGF-beta 1 downstream gene and promotes lung adenocarcinoma metastasis. Importantly, C/EBP delta caused significant oscillations in both lipid metabolic and epithelial to mesenchymal transition (EMT) gene networks. Mechanistically, we demonstrated that C/EBP delta recruited oncogene NCOA3 to transcriptionally activate Slug, a canonical EMT transcription factor, which in turn induced oxLDL receptor-1 (Lox1) expression and enhanced oxLDL uptake to promote cancer metastasis, which could be blocked with LOX1 neutralizing antibody. In summary, our results unveiled a previously unappreciated interplay between lipid metabolic and metastatic program, as well as the existence of a pivotal C/EBP delta-Slug-Lox1 transcription axis to promote oxLDL levels and cancer metastasis.