Little is known about how mutations in genes encoding tumor suppressors influence metastatic site selection and whether sustained inactivation of such genes influences tumor maintenance at these sites...

Using mouse pancreatic cancer models, Tsanov et al. show that reactivation of SMAD4 at metastatic sites promotes tumor growth in the lung through RUNX1 but restrains metastatic growth through KLF4 in the liver, influenced by organ-specific epigenetic states.