Advanced Science (Feb 2024)
Engrailed‐1 Promotes Pancreatic Cancer Metastasis
- Jihao Xu,
- Jae‐Seok Roe,
- EunJung Lee,
- Claudia Tonelli,
- Keely Y. Ji,
- Omar W. Younis,
- Tim D.D. Somervile,
- Melissa Yao,
- Joseph P. Milazzo,
- Herve Tiriac,
- Anna M. Kolarzyk,
- Esak Lee,
- Jean L. Grem,
- Audrey J. Lazenby,
- James A. Grunkemeyer,
- Michael A. Hollingsworth,
- Paul M. Grandgenett,
- Alexander D. Borowsky,
- Youngkyu Park,
- Christopher R. Vakoc,
- David A. Tuveson,
- Chang‐Il Hwang
Affiliations
- Jihao Xu
- Department of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USA
- Jae‐Seok Roe
- Department of Biochemistry Yonsei University Seoul 03722 South Korea
- EunJung Lee
- Department of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USA
- Claudia Tonelli
- Cold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USA
- Keely Y. Ji
- Department of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USA
- Omar W. Younis
- Department of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USA
- Tim D.D. Somervile
- Cold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USA
- Melissa Yao
- Cold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USA
- Joseph P. Milazzo
- Cold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USA
- Herve Tiriac
- Cold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USA
- Anna M. Kolarzyk
- Nancy E. and Peter C. Meinig School of Biomedical Engineering Cornell University Ithaca NY 14853 USA
- Esak Lee
- Nancy E. and Peter C. Meinig School of Biomedical Engineering Cornell University Ithaca NY 14853 USA
- Jean L. Grem
- Department of Medicine University of Nebraska Medical Center Omaha NE 68198 USA
- Audrey J. Lazenby
- Department of Medicine University of Nebraska Medical Center Omaha NE 68198 USA
- James A. Grunkemeyer
- Department of Medicine University of Nebraska Medical Center Omaha NE 68198 USA
- Michael A. Hollingsworth
- Department of Medicine University of Nebraska Medical Center Omaha NE 68198 USA
- Paul M. Grandgenett
- Department of Medicine University of Nebraska Medical Center Omaha NE 68198 USA
- Alexander D. Borowsky
- Department of Pathology School of Medicine University of California Davis Sacramento CA 95817 USA
- Youngkyu Park
- Cold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USA
- Christopher R. Vakoc
- Cold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USA
- David A. Tuveson
- Cold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USA
- Chang‐Il Hwang
- Department of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USA
- DOI
- https://doi.org/10.1002/advs.202308537
- Journal volume & issue
-
Vol. 11,
no. 6
pp. n/a – n/a
Abstract
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.
Keywords
- apoptosis
- cancer progression
- cancer therapeutics
- developmental transcription factor
- Engrailed‐1
- epigenetic reprogramming
