TY - JOUR
T1 - C/EBPδ-Slug-Lox1 axis promotes metastasis of lung adenocarcinoma via oxLDL uptake
AU - Wang, Dongmei
AU - Cheng, Xinghua
AU - Li, Yu
AU - Guo, Mingwei
AU - Zhao, Wenjun
AU - Qiu, Jin
AU - Zheng, Ying
AU - Meng, Meiyao
AU - Ping, Xiaodan
AU - Chen, Xin
AU - Wang, Shu
AU - Luo, Jian
AU - Luo, Qingquan
AU - Ma, Xinran
AU - Xu, Lingyan
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/1/23
Y1 - 2020/1/23
N2 - 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/EBPδ, a critical lipid metabolic regulator, is a TGF-β1 downstream gene and promotes lung adenocarcinoma metastasis. Importantly, C/EBPδ caused significant oscillations in both lipid metabolic and epithelial to mesenchymal transition (EMT) gene networks. Mechanistically, we demonstrated that C/EBPδ 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/EBPδ-Slug-Lox1 transcription axis to promote oxLDL levels and cancer metastasis.
AB - 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/EBPδ, a critical lipid metabolic regulator, is a TGF-β1 downstream gene and promotes lung adenocarcinoma metastasis. Importantly, C/EBPδ caused significant oscillations in both lipid metabolic and epithelial to mesenchymal transition (EMT) gene networks. Mechanistically, we demonstrated that C/EBPδ 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/EBPδ-Slug-Lox1 transcription axis to promote oxLDL levels and cancer metastasis.
UR - https://www.scopus.com/pages/publications/85073957533
U2 - 10.1038/s41388-019-1015-z
DO - 10.1038/s41388-019-1015-z
M3 - 文章
C2 - 31562393
AN - SCOPUS:85073957533
SN - 0950-9232
VL - 39
SP - 833
EP - 848
JO - Oncogene
JF - Oncogene
IS - 4
ER -
