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

Cancer Lett. 2011 Dec 15;312(1):55-61. doi: 10.1016/j.canlet.2011.07.024. Epub 2011 Aug 22.

Abstract

xCT, the functional subunit of the system x(c)(-) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System y+ / antagonists & inhibitors*
  • Amino Acid Transport System y+ / biosynthesis*
  • Amino Acid Transport System y+ / deficiency
  • Amino Acid Transport System y+ / genetics
  • Animals
  • Autophagy / physiology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • Glutathione / metabolism
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reactive Oxygen Species / metabolism*
  • Sulfasalazine / pharmacology
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • Amino Acid Transport System y+
  • RNA, Messenger
  • Reactive Oxygen Species
  • SLC7A11 protein, human
  • Sulfasalazine
  • Glutathione