PCK1 and colorectal carcinoma: Given our identification of PCK1 as a metabolic regulator of CRC liver metastatic colonization as well as the enrichment of a hypoxic signature by GSEA in highly metastatic PDXs, we speculated that perhaps PCK1 promotes metabolic adaptation that enables growth under hypoxia—a key feature of the hepatic microenvironment (Jungermann and Kietzmann, 2000; Dupuy et al., 2015) (Figure 6A).