Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.

Evidence has shown that tumor progression is associated with the acquisition of growing autonomy and the creation of a complex signaling network through various signal pathways. Which particular signaling pathway is involved in the metastasis of a specific cancer is unclear. Here, we applied metastatic functional screening and identified that one-carbon and SSP metabolism pathways, as well as related genes, are associated with tumor metastasis inhibition. We engineered the cancer cells with poorly or highly metastatic potential to confirm the metabolism pathways regulating the ability to colonize different tissue sites. We also asked whether the restriction of the metabolism pathways by known inhibitors. We then identified three new compounds that can inhibit the expression of these genes and block tumor metastasis. Our findings uncovered a mechanism by which tumor cells reprogram their metabolism to promote migration, invasion, and survival at distant sites in tumor metastasis, offering a rational strategy to guide clinical treatment. The identified novel molecular proteins and pathways represent a promising therapeutic target for metastatic disease.