NatD epigenetically activates FOXA2 expression to promote breast cancer progression by facilitating MMP14 expression.
NatD epigenetically activates FOXA2 expression to promote breast cancer progression by facilitating MMP14 expression.
复制标题
DOI：
10.1016/j.isci.2024.108840
复制
发表时间：
2024-02-16
期刊：
影响因子：
5.8
通讯作者：
Zhao, Quan
中科院分区：
文献类型：
--
作者：
Xing, Mengying;Yao, Bing;Xu, Jiaxuan;Lu, Peifen;Li, Qixiang;Wu, Dongliang;Chen, Bing;Wei, Jiwu;Su, Lei;Zhao, Quan
N-α-乙酰转移酶D （NatD）介导组蛋白H4 N-α-末端乙酰化（Nt-Ac-H4），但在乳腺癌转移中的作用尚不清楚。在这里，我们发现NatD的缺失直接抑制了FOXA2的表达，并伴随着FOXA2启动子上Nt-Ac-H4富集的显著减少。我们发现，NatD在原发性乳腺癌组织中普遍上调，其表达水平与FOXA2表达、侵袭性增强和不良临床结果相关。此外，我们发现FOXA2通过激活MMP14的表达来促进乳腺癌细胞的迁移和侵袭。MMP14在乳腺癌组织中也表达上调，其表达水平与FOXA2表达和不良临床预后相关。我们的研究表明，NatD- foxa2 - mmp14轴是促进乳腺癌细胞迁移和侵袭能力的关键信号通路，表明NatD是乳腺癌进展过程中细胞侵袭的关键表观遗传调节剂。NatD的上调与乳腺癌患者预后不良有关，NatD在体外和体内促进乳腺癌细胞迁移和侵袭，NatD催化FOXA2启动子的Nt-Ac-H4并促进其表达，FOXA2结合MMP14启动子并促进其表达；生物科学;系统生物学;癌症系统生物学；癌症
N-α-acetyltransferase D (NatD) mediates N-α-terminal acetylation of histone H4 (Nt-Ac-H4), but its role in breast cancer metastasis remains unknown. Here, we show that depletion of NatD directly represses the expression of FOXA2, and is accompanied by a significant reduction in Nt-Ac-H4 enrichment at the FOXA2 promoter. We show that NatD is commonly upregulated in primary breast cancer tissues, where its expression level correlates with FOXA2 expression, enhanced invasiveness, and poor clinical outcomes. Furthermore, we show that FOXA2 promotes the migration and invasion of breast cancer cells by activating MMP14 expression. MMP14 is also upregulated in breast cancer tissues, where its expression level correlates with FOXA2 expression and poor clinical prognosis. Our study shows that the NatD-FOXA2-MMP14 axis functions as a key signaling pathway to promote the migratory and invasive capabilities of breast cancer cells, suggesting that NatD is a critical epigenetic modulator of cell invasion during breast cancer progression. Upregulation of NatD is associated with poor prognosis in breast cancer patients NatD promotes breast cancer cell migration and invasion in vitro and in vivo NatD catalyzes the Nt-Ac-H4 of the FOXA2 promoter and promotes its expression FOXA2 binds to the promoter of MMP14 and promotes its expression Natural sciences; Biological sciences; Systems biology; Cancer systems biology; Cancer
登录
查看更多内容
NatD 通过阻止组蛋白 H4 丝氨酸磷酸化激活 Slug 表达来促进肺癌进展
影响因子：
16.6
作者：
Ju J;Chen A;Deng Y;Liu M;Wang Y;Wang Y;Nie M;Wang C;Ding H;Yao B;Gui T;Li X;Xu Z;Ma C;Song Y;Kvansakul M;Zen K;Zhang CY;Luo C;Fang M;Huang DCS;Allis CD;Tan R;Zeng CK;Wei J;Zhao Q
通讯作者：
Zhao Q
影响因子：
5.6
作者：
Ho YH;Chen L;Huang R
通讯作者：
Huang R
影响因子：
9.8
作者：
Arnesen T
通讯作者：
Arnesen T
HDAC2通过下调结直肠癌中的长非编码RNA H19抑制EMT介导的癌症转移
DOI：
10.1186/s13046-020-01783-9
发表时间：
2020-12-02
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Hu XT;Xing W;Zhao RS;Tan Y;Wu XF;Ao LQ;Li Z;Yao MW;Yuan M;Guo W;Li SZ;Yu J;Ao X;Xu X
通讯作者：
Xu X
影响因子：
10.5
作者：
Iwafuchi-Doi M;Zaret KS
通讯作者：
Zaret KS