Lysosomal membrane protein TMEM192 deficiency triggers crosstalk between             autophagy and apoptosis in HepG2 hepatoma cells.
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.
Department of Radiation Oncology, Qilu Hospital, and Department of Oncology, Shandong University School of Medicine, Shandong 250012, PR China.
Zhen
Z
Liu
Ya Juan
YJ
Lv
Yi Peng
YP
Song
Xiao Hong
XH
Li
Yuan Na
YN
Du
Cui Hong
CH
Wang
Li Kuan
LK
Hu
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009928:Organ Specificity; D021381:Protein Transport; D034622:RNA Interference; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C557523:transmembrane protein 192, human; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes