Xu, Jihao, Roe, Jae-Seok, Lee, EunJung, Tonelli, Claudia, Ji, Keely Y, Younis, Omar W, Somervile, Tim DD, Yao, Melissa, Milazzo, Joseph P, Tiriac, Herve, Kolarzyk, Anna M, Lee, Esak, Grem, Jean L, Lazenby, Audrey J, Grunkemeyer, James A, Hollingsworth, Michael A, Grandgenett, Paul M, Borowsky, Alexander D, Park, Youngkyu, Vakoc, Christopher R, Tuveson, David A, Hwang, Chang-Il (December 2023) Engrailed-1 Promotes Pancreatic Cancer Metastasis. Advanced Science. e2308537. ISSN 2198-3844
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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.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > pancreatic cancer diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL labs > Tuveson lab CSHL labs > Vakoc lab CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL Cancer Center Program > Cellular Communication in Cancer Program |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 18 December 2023 |
| Date Deposited: | 21 Dec 2023 13:41 |
| Last Modified: | 29 Apr 2024 20:05 |
| PMCID: | PMC10853725 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41359 |
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