The Role of Scavenging in Disease Dynamics

Contents Introduction................ 161 The Use of Animal Remains and the Exposure of Scavengers to Disease........ 163 The Relevance of Scavenging for Pathogens to Spread and Persist.......... 166 Human Related Factors Resulting in Increased Risk for Disease Transmission Through Scavenging.............. 170 Management of Scavenging to Reduce Disease Risks.............. 173 Restoration of Large Predators.................. 174 Elimination of Hunting of Scavengers............ 174 Destruction of Big Game and Domestic Animal Carcasses........... 174 Restoration of the Effects of Overabundance............. 175 Excluding Mammalian and Avian Scavengers from Natural Carrions.......... 176 Excluding Mammalian and Avian Scavengers from Vulture Restaurants........... 176 Conclusions and Future Perspectives........... 178 References............... 17

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure