However, according to our real-time PCR validation, the expression levels of these genes (PHGDH, PSAT1, PSPH, SHMT1/2, MTHFD1/2) did not change upon NRF2 silencing in HNSCC cells (Figure S19), suggesting that NRF2-mediated regulatory mechanisms may vary substantially in head and neck versus lung cancer, further supporting the unique role of NRF2-mediated G6PD and TKT expression in nucleotide biosynthesis of head and neck cancer. Here, MTHFD1 is linked to head and neck squamous cell carcinoma.