嵌入
癌症研究
同源盒
转录因子
增强子
胰腺癌
转移
体内
MAPK/ERK通路
生物
医学
癌症
基因
内科学
细胞生物学
信号转导
遗传学
作者
Jihao Xu,Jae‐Seok Roe,Eunjung Lee,C. Tonelli,Keely Ji,Ossama Younis,Tim D.D. Somervile,Melissa A. Yao,Joseph P. Milazzo,Hervé Tiriac,Anna M. Kolarzyk,Esak Lee,Jean L. Grem,Audrey J. Lazenby,James A. Grunkemeyer,Michael A. Hollingsworth,Paul M. Grandgenett,Alexander D. Borowsky,Young-Kyu Park,Christopher R. Vakoc,David A. Tuveson,Chang‐Il Hwang
标识
DOI:10.1002/advs.202308537
摘要
Abstract Engrailed‐1 (EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, it is reported that EN1 is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating roles in the activation of MAPK pathways and the acquisition of mesenchymal cell properties. Gain‐ and loss‐of‐function experiments demonstrated that EN1 promoted PDA transformation and metastasis in vitro and in vivo. The findings nominate the targeting of EN1 and downstream pathways in aggressive PDA.
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