Histone H2AX promotes metastatic progression by preserving glycolysis via hexokinase-2.
Histone H2AX promotes metastatic progression by preserving glycolysis via hexokinase-2.
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DOI：
10.1038/s41598-022-07675-6
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发表时间：
2022-03-08
影响因子：
4.6
通讯作者：
Weyemi U
中科院分区：
文献类型：
--
作者：
Liu Y;Li H;Wilson CN;Bai HJ;Boufraqech M;Weyemi U
Genomic stability is essential for organismal development, cellular homeostasis, and survival. The DNA double-strand breaks are particularly deleterious, creating an environment prone to cellular transformation and oncogenic activation. The histone variant H2AX is an essential component of the nucleosome responsible for initiating the early steps of the DNA repair process. H2AX maintains genomic stability by initiating a signaling cascade that collectively functions to promote DNA double-strand breaks repair. Recent advances have linked genomic stability to energetic metabolism, and alterations in metabolism were found to interfere with genome maintenance. Utilizing genome-wide transcripts profiling to identify differentially-expressed genes involved in energetic metabolism, we compared control and H2AX-deficient metastatic breast cancer cell lines, and found that H2AX loss leads to the repression of key genes regulating glycolysis, with a prominent effect on hexokinase-2 (HK2). These observations are substantiated by evidence that H2AX loss compromises glycolysis, effect which was reversed by ectopic expression of HK2. Utilizing models of experimental metastasis, we found that H2AX silencing halts progression of metastatic breast cancer cells MDA-MB-231. Most interestingly, ectopic expression of HK2 in H2AX-deficient cells restores their metastatic potential. Using multiple publicly available datasets, we found a significantly strong positive correlation between H2AX expression levels in patients with invasive breast cancer, and levels of glycolysis genes, particularly HK2. These observations are consistent with the evidence that high H2AX expression is associated with shorter distant metastasis-free survival. Our findings reveal a role for histone H2AX in controlling the metastatic ability of breast cancer cells via maintenance of HK2-driven glycolysis.
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影响因子：
21.3
作者：
Rezaeian AH;Li CF;Wu CY;Zhang X;Delacerda J;You MJ;Han F;Cai Z;Jeong YS;Jin G;Phan L;Chou PC;Lee MH;Hung MC;Sarbassov D;Lin HK
通讯作者：
Lin HK
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
8.8
作者：
Domaschenz, Renae;Kurscheid, Sebastian;Tremethick, David J.
通讯作者：
Tremethick, David J.
影响因子：
4
作者：
Dillekas, Hanna;Rogers, Michael S.;Straume, Oddhjorn
通讯作者：
Straume, Oddhjorn
DOI：
10.1073/pnas.1508871112
发表时间：
2015-09-15
影响因子：
11.1
作者：
Viticchie, Guiditta;Agostini, Massimiliano;Candi, Eleonora
通讯作者：
Candi, Eleonora