The gluconeogenic enzyme PCK1 and pyrimidine nucleotide biosynthetic enzyme DHODH drive hypoxic pyrimidine nucleotide biosynthesis and liver metastatic colonization in colorectal cancer, which is therapeutically exploitable by DHODH pharmacologic inhibition.
MYC and Twist1 drive metastasis by a novel non-cell-autonomous transcriptional mechanism of eliciting a cytokinome that mediates the crosstalk between cancer cells and macrophages, and its therapeutic blockade inhibits metastasis.
Inactivation of a multifunctional RNA-binding protein can lead to the acquisition of pro-metastatic phenotypes, possibly by stabilizing large-scale transcriptomic changes that provide a selective advantage during cancer progression.
Development and application of highly sensitive in situ transcriptomics method, Flura-seq, in identifying dynamic organ-specific transcriptomes in early stage breast cancer metastasis have been described.
Syngeneic tp53-null zebrafish develop a wide range of tumors that engraft into recipient animals with loss of Tp53 leading to increased metastasis in embryonal rhabdomyosarcoma (ERMS), likely accounting for increased aggression in TP53-inactivated human ERMS.
Colon cancer cells disseminate and colonize distant organ sites along the invasion-metastasis cascade by transiently activating intermediate epithelial to mesenchymal transition states through distinct transcriptional trajectories.