| RRC ID |
54226
|
| 著者 |
Hirata K, Takakura Y, Shibazaki M, Morii M, Honda T, Oshima M, Aoyama K, Iwama A, Nakayama Y, Takano H, Yamaguchi N, Yamaguchi N.
|
| タイトル |
Forkhead box protein A1 confers resistance to transforming growth factor-β-induced apoptosis in breast cancer cells through inhibition of Smad3 nuclear translocation.
|
| ジャーナル |
J Cell Biochem
|
| Abstract |
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.
|
| 公開日 |
2018-9-11
|
| DOI |
10.1002/jcb.27551
|
| PMID |
30206966
|
| IF |
3.448
|
| 引用数 |
2
|
| リソース情報 |
| 遺伝子材料 |
pCMFlag_hsSMAD3 (RDB07019) |
