Detail
Experiment ID:
EXP00170
Reference:
- Title: The oncogene metadherin modulates the apoptotic pathway based on the tumor necrosis factor superfamily member TRAIL (Tumor Necrosis Factor-related Apoptosis-inducing Ligand) in breast cancer.
- Author: Zhang N, Wang X, Huo Q, Li X, Wang H, Schneider P, Hu G, Yang Q
- Journal: The Journal of biological chemistry.2013 Mar 29;288(13):9396-407.doi:10.1074/jbc.M112.395913.
- Abstract: Metadherin (MTDH), the newly discovered gene, is overexpressed in more than 40% of breast cancers. Recent studies have revealed that MTDH favors an oncogenic course and chemoresistance. With a number of breast cancer cell lines and breast tumor samples, we found that the relative expression of MTDH correlated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity in breast cancer. In this study, we found that knockdown of endogenous MTDH cells sensitized the MDA-MB-231 cells to TRAIL-induced apoptosis both in vitro and in vivo. Conversely, stable overexpression of MTDH in MCF-7 cells enhanced cell survival with TRAIL treatment. Mechanically, MTDH down-regulated caspase-8, decreased caspase-8 recruitment into the TRAIL death-inducing signaling complex, decreased caspase-3 and poly(ADP-ribose) polymerase-2 processing, increased Bcl-2 expression, and stimulated TRAIL-induced Akt phosphorylation, without altering death receptor status. In MDA-MB-231 breast cancer cells, sensitization to TRAIL upon MTDH down-regulation was inhibited by the caspase inhibitor Z-VAD-fmk (benzyloxycarbonyl-VAD-fluoromethyl ketone), suggesting that MTDH depletion stimulates activation of caspases. In MCF-7 breast cancer cells, resistance to TRAIL upon MTDH overexpression was abrogated by depletion of Bcl-2, suggesting that MTDH-induced Bcl-2 expression contributes to TRAIL resistance. We further confirmed that MTDH may control Bcl-2 expression partly by suppressing miR-16. Collectively, our results point to a protective function of MTDH against TRAIL-induced death, whereby it inhibits the intrinsic apoptosis pathway through miR-16-mediated Bcl-2 up-regulation and the extrinsic apoptosis pathway through caspase-8 down-regulation.
- PMID: 23408429
Expression Profile:
- Description:microRNA profile of human nasopharyngeal tissues: nasopharyngeal carcinoma tissues vs. normal nasopharyngeal tissues
- Organism:Homo sapiens
- Source:GEO
- Source ID:GSE32960
- Platform: GPL14722
- Number of samples:330
- Overall design:microRNA profiling of nasopharyngeal carcinoma tissues vs. normal nasopharyngeal tissues312 paraffin-embedded nasopharyngeal carcinoma tissues and 18 paraffin-embedded normal nasopharyngeal tissues
- Instrument:microRNA array
Design and Sample:
- Cancer Type:nasopharyngeal cancer
- Cancer SubType:N/A
- Cell Line:N/A
- Experimental Design:cancer vs normal
- Case Sample:nasopharyngeal carcinoma
- Control Sample:normal nasopharyngeal tissue
- Num of Case:312
- Num of Control:18
- Quantification Software:Limma
- Num of miRNAs:872
Identification:
- Num of Up:230
- Num of Down:170
Time Info:
- Create Time2016-03-14
- Update Time:2021-05-27
Status:
| miRNA ID | Cancer Type | Design | logFC | AveExpr | T value | P value | adj Pvalue | Status | Plot |
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