SMAD4 represses FOSL1 expression and pancreatic cancer metastatic colonization

Cell Rep. 2021 Jul 27;36(4):109443. doi: 10.1016/j.celrep.2021.109443.

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.

Keywords: FOSL1; PDAC; SMAD4; colonization; metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Supplementary concepts

  • Pancreatic Carcinoma