Int J Med Sci 2017; 14(3):284-293. doi:10.7150/ijms.17861
Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2
1. Department of pathology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
2. Institute of Biochemistry, Microbiology, and Immunology, Chung Shan Medical University, Taichung City, Taiwan.
3. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City, Taiwan.
Huang BP, Lin CS, Wang CJ, Kao SH. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2. Int J Med Sci 2017; 14(3):284-293. doi:10.7150/ijms.17861. Available from http://www.medsci.org/v14p0284.htm
Tumor necrosis factor alpha (TNFα) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNFα on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNFα stimulus. We observed that HepG2 cell revealed a higher resistance to TNFα-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By using a label-free quantitative proteomic analysis, we found that 520 proteins were differentially expressed in the HepG2 cells exposed to TNFα, including 211 up-regulated and 309 down-regulated proteins. We further confirmed several proteins with significant expression change (TNFα/control ratio>2.0 or <0.5) by immunoblotting using specific antibodies. We also analyzed the differential expressed proteins using Gene ontology and KEGG annotations, and the results implicated that TNFα might regulate ribosome, spliceosome, antigen processing and presentation, and energy metabolism in HepG2 cells. Moreover, we demonstrated that upregulation of heat shock protein 70 (HSP70) was involved in both the promoted migration and the inhibited apoptosis of HepG2 cells in response to TNFα. Collectively, these findings indicate that TNFα alters protein expression such as HSP70, which triggering specific molecular processes and signaling cascades that promote migration and inhibit apoptosis of HepG2 cells.
Keywords: Hepatocellular carcinoma, Tumor necrosis factor-alpha, apoptosis, Label-free proteomic analysis