BNIP3 supports melanoma cell migration and vasculogenic mimicry by orchestrating the actin cytoskeleton
| العنوان: | BNIP3 supports melanoma cell migration and vasculogenic mimicry by orchestrating the actin cytoskeleton |
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| المؤلفون: | K Rillaerts, Dmitri V. Krysko, S Van Eygen, Abhishek D. Garg, Hannelore Maes, Peter Vandenabeele, Kris Nys, Tom Verfaillie, Patrizia Agostinis |
| المصدر: | Cell Death & Disease CELL DEATH & DISEASE |
| بيانات النشر: | Nature Publishing Group, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | 0301 basic medicine, rac1 GTP-Binding Protein, Cancer Research, Time Factors, TUMOR-CELLS, Melanoma, Experimental, CDC42, migration, Mice, Cell Movement, Medicine and Health Sciences, TRANSCRIPTIONAL REPRESSOR, Cytoskeleton, CD47, cdc42 GTP-Binding Protein, vasculogenic mimicry, DEATH, Cell migration, cytoskeleton, Cell biology, Mitochondria, Actin Cytoskeleton, Cdc42 GTP-Binding Protein, Original Article, RNA Interference, Signal Transduction, EXPRESSION, MITOCHONDRIAL DYSFUNCTION, BNIP3, Cell Survival, Immunology, FOCAL ADHESION KINASE, CD47 Antigen, Biology, RHO-GTPASES, Transfection, Adherens junction, Focal adhesion, Mitochondrial Proteins, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cell Line, Tumor, Proto-Oncogene Proteins, melanoma, Human Umbilical Vein Endothelial Cells, Animals, Humans, Vasculogenic mimicry, Neoplasm Invasiveness, Cell Shape, Focal Adhesions, Neuropeptides, Membrane Proteins, Cell Biology, Actin cytoskeleton, 030104 developmental biology, Cancer research, INTEGRIN-ASSOCIATED PROTEIN, Reactive Oxygen Species, GASTRIC-CANCER |
| الوصف: | BNIP3 is an atypical BH3-only member of the BCL-2 family of proteins with reported pro-death as well as pro-autophagic and cytoprotective functions, depending on the type of stress and cellular context. In line with this, the role of BNIP3 in cancer is highly controversial and increased BNIP3 levels in cancer patients have been linked with both good as well as poor prognosis. In this study, using small hairpin RNA (shRNA) lentiviral transduction to stably knockdown BNIP3 (BNIP3-shRNA) expression levels in melanoma cells, we show that BNIP3 supports cancer cell survival and long-term clonogenic growth. Although BNIP3-shRNA increased mitochondrial mass and baseline levels of reactive oxygen species production, which are features associated with aggressive cancer cell behavior, it also prevented cell migration and completely abolished the ability to form a tubular-like network on matrigel, a hallmark of vasculogenic mimicry (VM). We found that this attenuated aggressive behavior of these melanoma cells was underscored by severe changes in cell morphology and remodeling of the actin cytoskeleton associated with loss of BNIP3. Indeed, BNIP3-silenced melanoma cells displayed enhanced formation of actin stress fibers and membrane ruffles, while lamellopodial protrusions and filopodia, tight junctions and adherens junctions were reduced. Moreover, loss of BNIP3 resulted in re-organization of focal adhesion sites associated with increased levels of phosphorylated focal adhesion kinase. Remarkably, BNIP3 silencing led to a drop of the protein levels of the integrin-associated protein CD47 and its downstream signaling effectors Rac1 and Cdc42. These observations underscore that BNIP3 is required to maintain steady-state levels of intracellular complexes orchestrating the plasticity of the actin cytoskeleton, which is integral to cell migration and other vital processes stimulating cancer progression. All together these results unveil an unprecedented pro-tumorigenic role of BNIP3 driving melanoma cell's aggressive features, like migration and VM. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-4889 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::479ec05e8c3d4310953a2f5cb4220425Test http://europepmc.org/articles/PMC3973222Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....479ec05e8c3d4310953a2f5cb4220425 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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