SMAD4 represses FOSL1 expression and pancreatic cancer metastatic colonization

SUMMARY 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.
Graphical abstract
In brief Loss of SMAD4 is associated with poor outcome in pancreatic cancer. Using an in vivo, isogenic metastatic colonization assay, Dai et al. identified SMAD4-regulated genes that affect metastasis but not primary tumor growth. FOSL1 is a SMAD4-regulated gene that is necessary and sufficient to drive metastatic colonization.