细胞内
糖酵解
重编程
癌症研究
生物
癌症
细胞生物学
抑制器
癌细胞
转移
原癌基因酪氨酸蛋白激酶Src
NAD+激酶
生物化学
磷酸化
新陈代谢
细胞
遗传学
酶
作者
Wenwen Xue,Xin Li,Wuhao Li,Yixuan Wang,Cuiping Jiang,Lin Zhou,Jian Gao,Ying Yu,Yan Shen,Qiang Xu
标识
DOI:10.1038/s41392-021-00856-1
摘要
Abstract Loss-of-function mutations frequently occur in tumor suppressor genes, i.e., p53, during the malignant progression of various cancers. Whether any intrinsic suppressor carries a rare mutation is largely unknown. Here, we demonstrate that intracellular cytokine-like protein 1 (CYTL1) plays a key role in preventing the robust glycolytic switching characteristic of breast cancer. A low intracellular CYTL1 level, not its mutation, is required for metabolic reprogramming. Breast cancer cells expressing an intracellular form of CYTL1 lacking a 1-22 aa signal peptide, ΔCYTL1, show significantly attenuated glucose uptake and lactate production, which is linked to the inhibition of cell growth and metastasis in vitro and in vivo. Mechanistically, CYTL1 competitively binds the N-terminal sequence of NDUFV1 to block MDM2-mediated degradation by the proteasome, leading to the stability of the NDUFV1 protein. In addition to inducing increased NAD + levels, NDUFV1 interacts with Src to attenuate LDHA phosphorylation at tyrosine 10 and reduce lactate production. Our results reveal, for the first time, that CYTL1 is a novel tumor suppressor. Its function in reversing metabolic reprogramming toward glycolysis may be very important for the development of novel antitumor strategies.
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