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

Our previous findings demonstrated that SLC40A1 expression in hepatocellular carcinoma (HCC) tissue was significantly lower than para-tumor tissues and normal liver tissue. SLC40A1 expression was associated with tumor staging, intrahepatic metastasis and portal vein invasion. However, the mechanism of SLC40A1 as a modulator of autophagy involving the invasion and metastasis of HCC was not clear. In the present study, we found that SLC40A1 overexpressed in MHCC-97H could activate the autophagic flux and further inhibit cells' capacity of proliferation, migration, and invasion. Correspondingly, the autophagy inhibitor chloroquine could restrain the autophagic level of MHCC-97H-SLC40A1 cells and increase their invasive capacity. Moreover, SLC40A1 modulated the autophagic level of MHCC-97H via the AMPK/mTOR/ULK1 and AMPK/ULK1 signaling pathways. Our findings showed that elevated expression of SLC40A1 suppressed the invasion and metastasis of HCC via activating autophagy. Therapeutics that interfere with the expression of SLC40A1 in HCC cells and promotion of autophagy may attenuate tumor progression and metastasis.

Automated summary

In this study, we found that overexpression of SLC40A1 can inhibit the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells by activating the autophagy pathway. SLC40A1 regulates the autophagy level of MHCC-97H through the AMPK/mTOR/ULK1 and AMPK/ULK1 signaling pathways.