Lysosomal membrane protein TMEM192 deficiency triggers crosstalk between autophagy and apoptosis in HepG2 hepatoma cells

Oncol Rep. 2012 Sep;28(3):985-91. doi: 10.3892/or.2012.1881. Epub 2012 Jun 20.


As constituents of lysosomes, lysosomal membrane proteins play important roles in lysosome-related autophagy and apoptosis. In a recent proteomic study of lysosomal proteins, we identified transmembrane protein 192 (TMEM192) as a novel lysosomal membrane protein candidate. Using specific anti-TMEM192 antibody and lysosomal markers, the lysosomal localization of TMEM192 was determined by immunofluorescence. TMEM192 shows a wide expression pattern in mouse tissues. Interestingly, TMEM192 was found to be highly expressed in tumor cell lines, while it was not expressed or was detected at low levels in normal cell lines. By knockdown of TMEM192 expression using specific siRNAs, we found that TMEM192-deficient HepG2 hepatoma cells show growth inhibition and increased apoptosis. Autophagy was shown to be activated through detection of LC3II expression. Increased apoptosis was inhibited by blocking the expression of the key autophagy gene Atg7 in TMEM192-deficient HepG2 cells. The results suggest that TMEM192 is important for tumor cell growth and proliferation. TMEM192 deficiency can induce autophagy in tumor cells, and can further activate apoptosis by the mitochondrial pathway through autophagy. TMEM192 promotion of autophagy may be a new route for tumor therapy.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis*
  • Autophagy*
  • Autophagy-Related Protein 7
  • Gene Expression
  • Gene Knockdown Techniques
  • Hep G2 Cells
  • Humans
  • Lysosomes / metabolism*
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Organ Specificity
  • Protein Transport
  • RNA Interference
  • Ubiquitin-Activating Enzymes / genetics
  • Ubiquitin-Activating Enzymes / metabolism


  • Apoptosis Regulatory Proteins
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • transmembrane protein 192, human
  • ATG7 protein, human
  • Autophagy-Related Protein 7
  • Ubiquitin-Activating Enzymes