노재석 (연세대학교, Cold Spring Harbor Laboratory)

한빛사논문

조회668

연세대학교, Cold Spring Harbor Laboratory

CV File 206 kb

Adv. Sci., Dec 18 2023, | https://doi.org/10.1002/advs.202308537 Engrailed-1 Promotes Pancreatic Cancer Metastasis

Jihao Xu^1,2, Jae-Seok Roe^3,4, EunJung Lee ^1,4,5, Claudia Tonelli ^4,5, Keely Y Ji ¹, Omar W Younis ¹, Tim D D Somervile ⁴, Melissa Yao ^4,5, Joseph P Milazzo ⁴, Herve Tiriac ^4,5, Anna M Kolarzyk ⁶, Esak Lee ⁶, Jean L Grem ⁷, Audrey J Lazenby ⁷, James A Grunkemeyer ⁷, Michael A Hollingsworth ⁷, Paul M Grandgenett ⁷, Alexander D Borowsky⁸, Youngkyu Park^4,5, Christopher R Vakoc ⁴, David A Tuveson ^4,5, Chang-Il Hwang^1,2

¹Department of Microbiology and Molecular Genetics, University of California Davis, Davis, CA, 95616, USA.

²Comprehensive Cancer Center, University of California Davis, Sacramento, CA, 95817, USA.

³Department of Biochemistry, Yonsei University, Seoul, 03722, South Korea.

⁴Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA.

⁵Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY, 11724, USA.

⁶Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.

⁷Department of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA.

⁸Department of Pathology, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.

J.X. and J.S.R. contributed equally to this work.

CORRESPONDING AUTHORS : David A. Tuveson, Chang-Il Hwang

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.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-20)
연구진국내+국외 연구진
분야 생명과학 > 분자생물학

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