Engrailed-1 Promotes Pancreatic Cancer Metastasis

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:	Roe, Jae Seok Tonelli, Claudia Yao, Melissa Milazzo, Joseph Tiriac, Herve Lee, Eunjung Park, Youngkyu Vakoc, Christopher R. Tuveson, David A. Somervile, Tim
Communities:	CSHL labs > Tuveson lab CSHL labs > Vakoc lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	18 December 2023
Date Deposited:	21 Dec 2023 13:41
Last Modified:	11 Apr 2024 13:42
PMCID:	PMC10853725
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41359

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