Engrailed‐1 Promotes Pancreatic Cancer Metastasis
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 adenoc...
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-02-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202308537 |
| _version_ | 1797319251217874944 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jihao Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T04:04:13Z |
| format | Article |
| id | doaj.art-fa247bd53d254f95b68bf57810402255 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T04:04:13Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-fa247bd53d254f95b68bf578104022552024-02-09T08:26:35ZengWileyAdvanced Science2198-38442024-02-01116n/an/a10.1002/advs.202308537Engrailed‐1 Promotes Pancreatic Cancer MetastasisJihao Xu0Jae‐Seok Roe1EunJung Lee2Claudia Tonelli3Keely Y. Ji4Omar W. Younis5Tim D.D. Somervile6Melissa Yao7Joseph P. Milazzo8Herve Tiriac9Anna M. Kolarzyk10Esak Lee11Jean L. Grem12Audrey J. Lazenby13James A. Grunkemeyer14Michael A. Hollingsworth15Paul M. Grandgenett16Alexander D. Borowsky17Youngkyu Park18Christopher R. Vakoc19David A. Tuveson20Chang‐Il Hwang21Department of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USADepartment of Biochemistry Yonsei University Seoul 03722 South KoreaDepartment of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USACold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USADepartment of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USADepartment of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USACold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USACold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USACold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USACold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USANancy E. and Peter C. Meinig School of Biomedical Engineering Cornell University Ithaca NY 14853 USANancy E. and Peter C. Meinig School of Biomedical Engineering Cornell University Ithaca NY 14853 USADepartment of Medicine University of Nebraska Medical Center Omaha NE 68198 USADepartment of Medicine University of Nebraska Medical Center Omaha NE 68198 USADepartment of Medicine University of Nebraska Medical Center Omaha NE 68198 USADepartment of Medicine University of Nebraska Medical Center Omaha NE 68198 USADepartment of Medicine University of Nebraska Medical Center Omaha NE 68198 USADepartment of Pathology School of Medicine University of California Davis Sacramento CA 95817 USACold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USACold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USACold Spring Harbor Laboratory Cold Spring Harbor NY 11724 USADepartment of Microbiology and Molecular Genetics University of California Davis Davis CA 95616 USAAbstract 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.https://doi.org/10.1002/advs.202308537apoptosiscancer progressioncancer therapeuticsdevelopmental transcription factorEngrailed‐1epigenetic reprogramming |
| spellingShingle | 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 Engrailed‐1 Promotes Pancreatic Cancer Metastasis Advanced Science apoptosis cancer progression cancer therapeutics developmental transcription factor Engrailed‐1 epigenetic reprogramming |
| title | Engrailed‐1 Promotes Pancreatic Cancer Metastasis |
| title_full | Engrailed‐1 Promotes Pancreatic Cancer Metastasis |
| title_fullStr | Engrailed‐1 Promotes Pancreatic Cancer Metastasis |
| title_full_unstemmed | Engrailed‐1 Promotes Pancreatic Cancer Metastasis |
| title_short | Engrailed‐1 Promotes Pancreatic Cancer Metastasis |
| title_sort | engrailed 1 promotes pancreatic cancer metastasis |
| topic | apoptosis cancer progression cancer therapeutics developmental transcription factor Engrailed‐1 epigenetic reprogramming |
| url | https://doi.org/10.1002/advs.202308537 |
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