Suboptimal folic acid exposure rewires oncogenic metabolism and proteomics signatures to mediate human breast cancer malignancy

Probing Folate-Responsive and Stage-Sensitive Metabolomics and Transcriptional Co-Expression Network Markers to Predict Prognosis of Non-Small Cell Lung Cancer Patients

“…Furthermore, glucose flux analysis revealed that glutamine serves as the important precursor for glutathione synthesis, a key cellular antioxidant, critical for redox homeostasis and lung cancers progression [ 52 , 53 ]. Glutamine elevation to maintain redox homeostasis could be the prioritized metabolic choice of LF tumours under oxidative stress [ 54 , 55 ] for survival from oxidative signalling-apoptosis [ 9 ] and for malignant LC progression [ 53 ]. In line with the metabolic readout for LF-modifying glutamine-metabolizing genetic expression, glutathione metabolism ranked in the top two enriched pathway in LF but not in HF tumours in a stage-dependent manner.…”

“…Folate-mediated one-carbon metabolism contributes to multiple biochemical pathways of nucleotide biosynthesis, amino acid homeostasis [ 2 ], redox homeostasis [ 3 , 4 ], and epigenetic regulation to support normal growth and mass expansion of organism [ 5 ]. Cellular and animal studies has shown that folate restriction enhanced migration, invasiveness, and anchorage-independent oncospheroid formation in human colon [ 6 , 7 ], lungs [ 8 ], and human breast cancers [ 9 ]. However, supplemental high folate did not offset folate deprived-metabolic perturbation, but further promoted metastatic potentials of lung cancer cells and mouse tumours [ 10 , 11 ].…”