Hypoxia facilitates triple-negative breast cancer stem cells enrichment and stemness maintenance through oxidized ataxia telangiectasia mutated-induced one-carbon metabolism

Figure 7 Oxidized ataxia telangiectasia mutated sustains triple-negative breast cancer-cancer stem cells stemness via serine hydroxymethyltransferase 2- and methylenetetrahydrofolate dehydrogenase 2-mediated one-carbon metabolism. A: NADPH/NADP+ ratio in cancer stem cells (CSCs) under hypoxia compared with normoxia; B and C: NADPH/NADP+ ratio decreased in CSCs after Ku60019 treatment (B) or shc-Myc knockdown (C); D-F: Effects of one-carbon metabolite supplementation on mammosphere size (D) and number (E and F) in CSCs with serine hydroxymethyltransferase 2 (SHMT2) knockdown or methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) knockdown; G: Western blot analysis of MTHFD2, SHMT2, Kruppel-like factor 4, and sex-determining region Y-box 2 expression following SHMT2 or MTHFD2 knockdown under hypoxia. Data were presented as mean ± SD (n = 3). ^aP < 0.05. MTHFD2: Methylenetetrahydrofolate dehydrogenase 2; SHMT2: Serine hydroxymethyltransferase 2; KLF4: Kruppel-like factor 4; SOX2: Sex-determining region Y-box 2.