Disruption of xCT inhibits cell growth via the ROS/autophagy pathway in hepatocellular carcinoma

xCT, the functional subunit of the system xc- which plays an important role in maintaining intracellular glutathione (GSH) levels, is expressed in various malignant tumors. Here, we demonstrated that xCT expression is often elevated in HCC and is associated with poor prognosis in HCC patients; moreover, disruption of xCT suppressed HCC cell growth both in vitro and in vivo. xCT dysfunction has also been shown to increase intracellular reactive oxygen species (ROS) levels, thus in turn led to autophagic cell death of HCC cells. Taken together, these findings suggest that xCT may be a promising therapeutic target for human HCC.

► xCT is upregulated in HCC and is associated with poor prognosis of HCC patients.
► The disruption of xCT inhibits HCC cell proliferation in vitro and in vivo.
► The xCT blockades induce autophagy by increasing the ROS levels in HCC cells.