Overexpression of SLC40A1 inhibits the malignancy of hepatocellular carcinoma MHCC-97H cells by stimulation of autophagy

•The overexpression of SLC40A1 will activate the autophagy flux and up-regulate autophagy by promoting the formation of autophagosomes.•Overexpression of SLC40A1 can inhibit the proliferation, migration and invasion of liver cancer cells MHCC-97H.•SLC40A1 up-regulates autophagy through AMPK/mTOR/ULK1 and AMPK/ULK1 signaling pathways.•The expression of SLC40A1 will affect the iron content in the cell, and iron will affect energy production through the oxidized respiratory chain. AMPK is also an energy-sensing factor in cells. Increased AMP:ATP ratio activates AMPK. The activated AMPK up-regulates the level of autophagy through AMPK/mTOR/ULK1 and AMPK/ULK1 signaling pathways to meet the cell's energy requirements. While SLC40A1 overexpression positively regulates autophagy, it also reduces the proliferation, metastasis and invasion of liver cancer cells MHCC-97H. This tendency is significantly weakened after autophagy is inhibited. The expression level of SLC40A1 affects the intracellular iron content and thus the AMPK activity.