Abstract
High mobility group A2 (HMGA2) is closely related to the occurrence, development and prognosis of tumors. But the mechanism is unclear. Metabolic reprogramming is a dominant way to meet anabolic and energy requirements of tumor cells for their survival, growth and proliferation. Here, we investigated the role of metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis mediated by HMGA2/autophagy axis in cadmium (Cd, CdCl2)-induced migration. First, we found that Cd induced glycolysis and reduced OXPHOS in vivo (0.5 and 1 mg/kg, i.p. or 0.8 and 1.6 μM, i.t.) and in vitro (2 μM in A549 cells and 0.05 μM in HELF cells). Then, genetic knockdown of HMGA2 restored Cd-reduced mitochondrial mass and OXPHOS and inhibited Cd-increased glycolysis, indicating that HMGA2 was involved in Cd-induced metabolic reprogramming. 2-Deoxy-d-glucose (2DG, 5 mM), the inhibitor of glycolysis decreased Cd/HMGA2-induced cell migration and restored Cd/HMGA2-decreased OXPHOS and mitochondrial mass. Inhibition of autophagy by 3-Methyladenine (3MA, 3 mM) elucidated an essential role of autophagy in HMGA2-induced glycolysis, migration, and HMGA2-reduced OXPHOS. Overall, our study demonstrated that autophagy was required for HMGA2-mediated metabolic reprogramming, which was critical for Cd-induced migration. Targeting HMGA2 and autophagy-dependent reprogrammed metabolism may be an effective way to inhibit Cd-induced cell migration.