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Interferon-α sensitizes human gastric cancer cells to TRAIL-induced apoptosis via activation of the c-CBL-dependent MAPK/ERK pathway
| Content Provider | Scilit |
|---|---|
| Author | Qu, Jinglei Zhao, Mingfang Teng, Yuee Zhang, Ye Hou, Kezuo Jiang, Youhong Yang, Xianghong Shang, Hong Qu, Xiujuan Liu, Yunpeng |
| Copyright Year | 2011 |
| Description | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family that induces apoptosis in cancer cells. However, gastric cancer cells are insensitive to TRAIL. In the present study, we show that pretreatment with IFN-α enhanced TRAIL-induced apoptosis of gastric cancer MGC803 cells. IFN-α up-regulated death receptor 5 (DR5) expression and down-regulated survivin expression. Furthermore, extracellular-regulated protein kinase (ERK1/2) activation was induced by IFN-α, and a combination of IFN-α and TRAIL led to further activation of ERK1/2. Inhibition of the MAPK/ERK signaling pathway partially reversed apoptosis, as well as the expression patterns of DR5 and survivin. Moreover, the expression of the c-casitas B-lineage lymphoma (c-Cbl) family was down-regulated by IFN-α. Transfection of c-Cbl suppressed IFN-α-induced ERK activation. These results indicate that IFN-α enhances TRAIL-induced apoptosis in gastric cancer cells at least partially via downregulation of c-Cbl, and subsequent up-regulation of the MAPK/ERK pathway. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/cbt.12.6.15973?needAccess=true |
| Ending Page | 502 |
| Page Count | 9 |
| Starting Page | 494 |
| ISSN | 15384047 |
| e-ISSN | 15558576 |
| DOI | 10.4161/cbt.12.6.15973 |
| Journal | Cancer Biology & Therapy |
| Issue Number | 6 |
| Volume Number | 12 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2011-09-15 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry and Molecular Biology Protein Gastric Cancer Cancer Cells Induced Apoptosis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Pharmacology Molecular Medicine Oncology |
