A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer.
A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer.
复制标题
DOI：
10.1038/s41388-017-0023-0
复制
发表时间：
2018-03
期刊：
影响因子：
8
通讯作者：
Howe PH
中科院分区：
文献类型：
--
作者：
Howley BV;Link LA;Grelet S;El-Sabban M;Howe PH
为了更好地了解乳腺癌转移的过程，我们产生了一系列乳腺上皮细胞系，这些细胞系的侵袭性越来越强，转移到肺部。在这里，我们证明了在转移细胞中，内质网(ER)对高尔基体运输基因信号的上调增强了转运动力学，从而促进了恶性进展。我们观察到，在转移到肺的细胞中，ER-高尔基体转运增加，分泌体改变，对逆行转运抑制剂布雷菲尔丁A(BFA)敏感。CREB3被认为是上调的ER-高尔基体运输基因ARF4、COPB1和USO1的转录调节因子，这些基因的沉默在体外减少了转移表型，在体内减少了肺定植。此外，在乳腺癌患者中，高转移基因的表达与远处转移风险的增加、无复发和总生存率的降低显著相关，提示ER-高尔基转移的调控在转移进展中起着重要作用。
In order to better understand the process of breast cancer metastasis, we have generated a mammary epithelial progression series of increasingly aggressive cell lines that metastasize to lung. Here, we demonstrate that up-regulation of an Endoplasmic Reticulum (ER) to Golgi trafficking gene signature in metastatic cells enhances transport kinetics, which promotes malignant progression. We observe increased ER-Golgi trafficking, an altered secretome and sensitivity to the retrograde transport inhibitor brefeldin A (BFA) in cells that metastasize to lung. CREB3 was identified as a transcriptional regulator of up-regulated ER-Golgi trafficking genes ARF4, COPB1 and USO1, and silencing of these genes attenuated the metastatic phenotype in vitro and lung colonization in vivo. Furthermore, high trafficking gene expression significantly correlated with increased risk of distant metastasis and reduced relapse-free and overall survival in breast cancer patients, suggesting that modulation of ER-Golgi trafficking plays an important role in metastatic progression.
登录
查看更多内容
影响因子：
3.7
作者：
Hussey GS;Link LA;Brown AS;Howley BV;Chaudhury A;Howe PH
通讯作者：
Howe PH
影响因子：
--
作者：
CLERMONT, Y;XIA, L;HERMO, L
通讯作者：
HERMO, L
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D
影响因子：
48
作者：
Boncompain, Gaelle;Divoux, Severine;Perez, Franck
通讯作者：
Perez, Franck
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel