Artikel ; Online: Activation of TRPM7 by naltriben enhances migration and invasion of glioblastoma cells.
2017 Band 8, Heft 7, Seite(n) 11239–11248
Abstract: ... the TRPM7 activator naltriben on GBM viability, migration, and invasiveness. First, using the whole-cell ... significantly enhanced U87 cell migration and invasion (assessed with scratch wound assays, Matrigel invasion ... patch-clamp technique, we showed that naltriben enhanced the endogenous TRPM7-like current in U87 cells. In addition ...
| Abstract | Glioblastoma (GBM), the most common and aggressive brain tumor in the central nervous system, remains a lethal diagnosis with a median survival of < 15 months. Aberrant expression of the TRPM7 channel has been linked to GBM functions. In this study, using the human GBM cell line U87, we evaluated the TRPM7 activator naltriben on GBM viability, migration, and invasiveness. First, using the whole-cell patch-clamp technique, we showed that naltriben enhanced the endogenous TRPM7-like current in U87 cells. In addition, with Fura-2 Ca2+ imaging, we observed robust Ca2+ influx following naltriben application. Naltriben significantly enhanced U87 cell migration and invasion (assessed with scratch wound assays, Matrigel invasion experiments, and MMP-2 protein expression), but not viability and proliferation (evaluated with MTT assays). Using Western immunoblots, we also detected the protein levels of p-Akt/t-Akt, and p-ERK1|2/t-ERK1|2. We found that naltriben enhanced the MAPK/ERK signaling pathway, but not the PI3k/Akt pathway. Therefore, potentiated TRPM7 activity contributes to the devastating migratory and invasive characteristics of GBM. |
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| Mesh-Begriff(e) | Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Calcium/metabolism ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Immunoblotting ; Matrix Metalloproteinase 2/metabolism ; Membrane Potentials/drug effects ; Naltrexone/analogs & derivatives ; Naltrexone/pharmacology ; Neoplasm Invasiveness ; Patch-Clamp Techniques ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; TRPM Cation Channels/metabolism |
| Chemische Substanzen | TRPM Cation Channels ; naltrindole benzofuran (111555-58-9) ; Naltrexone (5S6W795CQM) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Calcium (SY7Q814VUP) |
| Sprache | Englisch |
| Erscheinungsdatum | 2017-01-04 |
| Erscheinungsland | United States |
| Dokumenttyp | Journal Article |
| ZDB-ID | 2560162-3 |
| ISSN | 1949-2553 ; 1949-2553 |
| ISSN (online) | 1949-2553 |
| ISSN | 1949-2553 |
| DOI | 10.18632/oncotarget.14496 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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