Engrailed-1 Promotes Pancreatic Cancer Metastasis.
Jihao XuJae-Seok RoeEunJung LeeClaudia TonelliKeely Y JiOmar W YounisTim D D SomervileMelissa YaoJoseph P MilazzoHerve TiriacAnna M KolarzykEsak LeeJean L GremAudrey J LazenbyJames A GrunkemeyerMichael A HollingsworthPaul M GrandgenettAlexander D BorowskyYoungkyu ParkChristopher R VakocDavid A TuvesonChang-Il HwangPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
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.
Keyphrases
- transcription factor
- genome wide
- signaling pathway
- genome wide identification
- poor prognosis
- single cell
- type diabetes
- metabolic syndrome
- oxidative stress
- gene expression
- cell proliferation
- adipose tissue
- dna methylation
- long non coding rna
- blood brain barrier
- dna binding
- cell therapy
- binding protein
- weight loss
- brain injury