Fig. 3: Oxidized ATM induces EMR of CSC.

a Metabonomics analysis was performed to identify the changed metabolites between oxidized ATM-activated CSC and -inactivated CSC derived from Hs578T under hypoxia, and relative metabolic signaling pathways were enriched by KEGG analysis. Ratio represented the number of changed metabolites to the total number of metabolites in the pathway. b–i Hs578T and BT549 cells, and ATM-silenced Hs578T and BT549 cells were suspended in culture in CSC medium under hypoxia and treated with or without indicated reagents (e.g., 2-deoxyglucose (2-DG, 5 mM), metformin (3 mM), and/or KU60019 (10 µM)). The relative of ATP products (b) and metabolic index were checked. Glucose consumption of mammospheres (c); the productions of pyruvate (d), lactate (e), acetyl-CoA (f), citrate (g), succinate (h), and fumarate (i) were shown. j CSC incorporation of ¹³C₆-labeled glucose was added into CSC medium and pulsed for up to 8 h; the isotopolog distribution for pyruvate, citrate, succinate, and fumarate with two ¹³C atoms in sphere cells was shown. k–m CSCs were treated with or without BMS303141 (an inhibitor of ATP-citrate lyase, 20 μM); lactate, succinate, cytosolic, and mitochondrial acetyl-CoA concentrations were determined (*P < 0.05, **P < 0.01).