Inhibition of either BRD4 or MTHFD1 results in similar changes in nuclear metabolite composition and gene expression; pharmacological inhibitors of the two pathways synergize to impair cancer cell viability in vitro and in vivo.
These results demonstrate that MTHFD1 and SHMT1, which are key enzymes providing one-carbon units for dTMP biosynthesis in the form of 5,10-methylenetetrahydrofolate, are direct targets of As<sub>2</sub>O<sub>3</sub>-induced proteolytic degradation, providing a mechanism for arsenic in the etiology of cancer and developmental anomalies.
Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between the MTHFD1 polymorphisms and cancer risk.