SMAD4 represses FOSL1 expression and pancreatic cancer metastatic colonization.

Abstract

Metastasis is a complex and poorly understood process. In pancreatic cancer, loss of the transforming growth factor (TGF)-β/BMP effector SMAD4 is correlated with changes in altered histopathological transitions, metastatic disease, and poor prognosis. In this study, we use isogenic cancer cell lines to identify SMAD4 regulated genes that contribute to the development of metastatic colonization. We perform an in vivo screen identifying FOSL1 as both a SMAD4 target and sufficient to drive colonization to the lung. The targeting of these genes early in treatment may provide a therapeutic benefit.

• Authors: Chao Dai, Jonathan P Rennhack, Taylor E Arnoff, Maneesha Thaker, Scott T Younger, John G Doench, August Yue Huang, Annan Yang, Andrew J Aguirre, Belinda Wang, Evan Mun, Joyce T O'Connell, Ying Huang, Katherine Labella, Jessica A Talamas, Ji Li, Nina Ilic, Justin Hwang, Andrew L Hong, Andrew O Giacomelli, Ole Gjoerup, David E Root, William C Hahn
• Journal: Cell reports (Cell Rep) Vol. 36 Issue 4 Pg. 109443 (07 27 2021) ISSN: 2211-1247 [Electronic] United States
• PMID: 34320363 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Proto-Oncogene Proteins c-fos
• SMAD4 protein, human
• Smad4 Protein
• fos-related antigen 1

Topics

• Adenocarcinoma (genetics, pathology)
• Animals
• Carcinoma, Pancreatic Ductal (genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Enhancer Elements, Genetic (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• Neoplasm Metastasis
• Pancreatic Neoplasms (genetics, pathology)
• Proto-Oncogene Proteins c-fos (genetics, metabolism)
• Smad4 Protein (metabolism)
• Pancreatic Neoplasms