The thioredoxin system in breast cancer cell invasion and migration
| العنوان: | The thioredoxin system in breast cancer cell invasion and migration |
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| المؤلفون: | Kathryn F. Tonissen, Maneet Bhatia, Giovanna Di Trapani, Mallory M. King, Kelly L. McGrath, Fenil Shah, F.M. Clarke, Pornpimol Charoentong |
| المصدر: | Redox Biology, Vol 8, Iss C, Pp 68-78 (2016) Redox Biology |
| بيانات النشر: | The Authors. Published by Elsevier B.V. |
| مصطلحات موضوعية: | RFU, relative fluorescence units, 0301 basic medicine, Clinical Biochemistry, Gene Expression, TXNIP, thioredoxin interacting protein, Biochemistry, H2DCF-DA, 2′,7′-dichlorodihydrofluorescein diacetate, Metastasis, Thioredoxins, 0302 clinical medicine, Breast cancer, Cell Movement, Trx, thioredoxin, lcsh:QH301-705.5, GFP, green fluorescent protein, TCGA, the cancer genome atlas, lcsh:R5-920, MTT, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Cell migration, Prognosis, VEGF, vascular endothelial growth factor, Cell invasion, ATL, adult T-cell leukemia, MMP, matrix metalloproteinase, 030220 oncology & carcinogenesis, Female, TIMP, tissue inhibitor of metalloproteinase, Thioredoxin, lcsh:Medicine (General), Oxidation-Reduction, Research Paper, medicine.drug, Thioredoxin Reductase 1, TrxR, thioredoxin reductase, Auranofin, Cell Survival, TNB, 2-nitro-5-thiobenzoate anion, Breast Neoplasms, Biology, OS, overall survival, 03 medical and health sciences, ROS, reactive oxygen species, TPM, transcripts per million, FBS, fetal bovine serum, Cell Line, Tumor, HUVEC, human umbilical vein endothelial cells, medicine, Humans, Cell Proliferation, DTNB, 5,5′-Dithio-Bis (2-Nitrobenzoic Acid), Cell growth, Gene Expression Profiling, Organic Chemistry, Cancer, medicine.disease, HR, hazard ratio, CI, confidence interval, DFS, disease free survival, 030104 developmental biology, lcsh:Biology (General), DTT, dithiothreitol, Cancer cell, Immunology, Cancer research, Patient survival, DMFS, distant-metastasis free survival, Extracellular Space, Reactive Oxygen Species, Transcriptome |
| الوصف: | Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1) in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1) expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS) or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS) levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration. Graphical abstract fx1 Highlights • Over expression of thioredoxin in MDA-MB-231 cells enhanced cell invasion in vitro. • Thioredoxin inhibition reduced cell invasion and migration of MDA-MB-231 cells. • Addition of thioredoxin enhanced migration of MDA-MB-231 cells in vitro. • Auranofin treatment inhibited MDA-MB-231 cell migration and clonogenic activity. • High Trx1 and TrxR1 expression is associated with a poor breast cancer prognosis. |
| اللغة: | English |
| تدمد: | 2213-2317 |
| DOI: | 10.1016/j.redox.2015.12.004 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a1bbe4ecc6f7479b84181edf4ab715bTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2a1bbe4ecc6f7479b84181edf4ab715b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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| DOI: | 10.1016/j.redox.2015.12.004 |