ArticleThe Journal of biological chemistry2013
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.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Current Update on Categorization of Migraine Subtypes on the Basis of Genetic Variation: a Systematic Review.Molecular neurobiology · 2024Pooled it
- Association of MTDH immunohistochemical expression with metastasis and prognosis in female reproduction malignancies: a systematic review and meta-analysis.Scientific reports · 2016Pooled it
- Trial
- MicroRNA-122 overexpression suppresses the colon cancer cell proliferation by downregulating the astrocyte elevated gene-1/metadherin oncoprotein.Annals of medicine · 2025Article
- Review
- Promotion of tumorigenesis by miR-1260b-targeting CASP8: Potential diagnostic and prognostic marker for breast cancer.Cancer science · 2022Article
- Review
- Knockdown of long noncoding RNA TP73-AS1 suppresses the malignant progression of breast cancer cells in vitro through targeting miRNA-125a-3p/metadherin axis.Thoracic cancer · 2020Article
- Berberine Inhibits Proliferative Ability of Breast Cancer Cells by Reducing Metadherin.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Functional Prediction of Candidate MicroRNAs for CRC Management Using in Silico Approach.International journal of molecular sciences · 2019Article
- SREBP1, targeted by miR-18a-5p, modulates epithelial-mesenchymal transition in breast cancer via forming a co-repressor complex with Snail and HDAC1/2.Cell death and differentiation · 2019Article
- Neuroprotective effect of (-)-epigallocatechin-3-gallate on autoimmune thyroiditis in a rat model by an anti-inflammation effect, anti-apoptosis and inhibition of TRAIL signaling pathway.Experimental and therapeutic medicine · 2018Article
- Chelerythrine chloride induces apoptosis in renal cancer HEK-293 and SW-839 cell lines.Oncology letters · 2016Article
- Solamargine triggers hepatoma cell death through apoptosis.Oncology letters · 2015Article
- Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin.PloS one · 2015Article
- Candidate pathways and genes for nasopharyngeal carcinoma based on bioinformatics study.International journal of clinical and experimental pathology · 2015Article
- Huaier Extract Induces Autophagic Cell Death by Inhibiting the mTOR/S6K Pathway in Breast Cancer Cells.PloS one · 2015Article
- RNA interference-mediated knockdown of astrocyte elevated gene-1 inhibits growth, induces apoptosis, and increases the chemosensitivity to 5-fluorouracil in renal cancer Caki-1 cells.Molecules and cells · 2014Article
- MTDH mediates trastuzumab resistance in HER2 positive breast cancer by decreasing PTEN expression through an NFκB-dependent pathway.BMC cancer · 2014Article
- Progress of cancer research on astrocyte elevated gene-1/Metadherin (Review).Oncology letters · 2014Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
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.
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