Forkhead box protein A1 confers resistance to transforming growth factor‐β‐induced apoptosis in breast cancer cells through inhibition of Smad3 nuclear translocation
Forkhead box protein A1 confers resistance to transforming growth factor‐β‐induced apoptosis in breast cancer cells through inhibition of Smad3 nuclear translocation
复制标题
叉头盒蛋白 A1 通过抑制 Smad3 核易位赋予乳腺癌细胞抵抗转化生长因子-β 诱导的细胞凋亡的能力
DOI：
10.1002/jcb.27551
复制
发表时间：
2018
影响因子：
4
通讯作者：
Yamaguchi Noritaka
中科院分区：
文献类型：
--
作者：
Hirata Kensuke;Takakura Yuki;Shibazaki Misato;Morii Mariko;Honda Takuya;Oshima Motohiko;Aoyama Kazumasa;Iwama Atsushi;Nakayama Yuji;Takano Hiroyuki;Yamaguchi Naoto;Yamaguchi Noritaka
转化生长因子-β（TGF-β）诱导正常上皮细胞（如乳腺上皮）的凋亡。虽然乳腺癌进展与获得对TGF-β诱导的细胞凋亡的抗性有关，但这种抗性的分子机制在很大程度上是未知的。在这里，我们表明，叉头框蛋白A1（FOXA 1），这是已知的先驱转录因子，抑制TGF-β诱导的雌激素受体阳性乳腺癌细胞的凋亡。研究发现FOXA 1通过抑制Smad 3与核输入受体importin 7的结合，抑制Smad 3（TGF-β信号传导下游的关键转录因子）的核转位。此外，RNA测序分析表明，敲低FOXA 1上调Smad 3介导的促凋亡基因表达。这些结果表明，FOXA 1作为一种有效的生存因子，通过抑制雌激素受体阳性乳腺癌细胞中的Smad 3信号传导来抑制TGF-β诱导的细胞凋亡。因此，我们第一次提供了证据，即位于细胞质的FOXA 1在TGF-β介导的信号转导中负调控Smad 3诱导的细胞凋亡。
Transforming growth factor‐β (TGF‐β) induces apoptosis of normal epithelial cells, such as mammary epithelium. Although breast cancer progression associates with acquisition of resistance to TGF‐β‐induced apoptosis, the molecular mechanisms underlying this resistance are largely unknown. Here, we show that forkhead box protein A1 (FOXA1), which is known as a pioneer transcription factor, suppresses TGF‐β‐induced apoptosis of estrogen receptor–positive breast cancer cells. FOXA1 is found to inhibit nuclear translocation of Smad3, a key transcription factor downstream of TGF‐β signaling, through suppression of the binding of Smad3 to the nuclear import receptor importin7. Furthermore, RNA sequencing analyses show that knockdown of FOXA1 upregulates Smad3‐mediated proapoptotic gene expression. These results demonstrate that FOXA1 as a potent survival factor that suppresses TGF‐β‐induced apoptosis by inhibiting Smad3 signaling in estrogen receptor–positive breast cancer cells. Thus, we provide evidence for the first time that FOXA1 localizing to the cytoplasm negatively regulates Smad3‐induced apoptosis in TGF‐β‐mediated signal transduction.
转化生长因子β3 在乳腺退化的第一阶段诱导细胞死亡。
DOI：
10.1242/dev.127.14.3107
发表时间：
2000
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Nguyen,AV;Pollard,JW
通讯作者：
Pollard,JW
KRAB 相关蛋白 1 (KAP1) 在 Tyr-449、Tyr-458 和 Tyr-517 处被核酪氨酸激酶磷酸化，抑制 KAP1 和异染色质蛋白 1α (HP1α) 与异染色质的关联
影响因子：
4.8
作者：
Kubota;S.;Fukumoto;Y.;Aoyama;K.;Ishibashi;K.;Yuki;R.;Morinaga;T.;Honda;T.;Yamaguchi;N.;Hashimoto;Y.;Kuga;T.;Tomonaga T;and Yamaguchi;N
通讯作者：
N