Autophagy induces mTOR-dependent glucose uptake and mTOR-independent lactate utilization in cadmium-treated A549 cells.

Cadmium (Cd) is a non-essential heavy metal with many harmful effects, especially tumorigenesis. Previously we established that autophagy-dependent increasing of glycolysis played an important role in Cd-induced cell growth and migration of A549 and HELF cells. In this study, we found Cd could induce autophagy and mTOR in A549 cells, HELF cells and in lung tissues of BALB/c mice. More interestingly, Cd-induced elevation of mTOR was autophagy-dependent and autophagy-induced cell growth and glycolysis was mTOR-dependent. However, in A549 cells, besides the above mTOR-dependent pathway, Cd-induced autophagy could directly induce PKM2 and LDHA independent of mTOR. Further study showed that only in A549 cells could autophagy other than mTOR enable Cd to increase MCT1 expression and MCT1 was involved in autophagy-induced PKM2 and LDHA. Sodium lactate added in the culture medium promoted Cd-induced cell growth of A549 cells, while had no effect on HELF cells. Finally, the effect of autophagy/MCT1/PKM2 pathway on lactate utilization to facilitate Cd-induced A549 cell growth was determined. Above all, we concluded that in HELF cells, autophagy induced mTOR-dependent glycolysis in which GLUT1 and HKII was elevated to promote glucose intake to accelerate cell growth. Whereas, in A549 cells, besides the above pathway to use glucose, autophagy could induce an mTOR-independent glycolysis pathway in which lactate could be used as fuel through autophagy-MCT1-PKM2 to escape glucose deficiency.