Article ; Online: Augmentation of invadopodia formation in temozolomide-resistant or adopted glioma is regulated by c-Jun terminal kinase-paxillin axis.
Biochemical and biophysical research communications
2015 Volume 468, Issue 1-2, Page(s) 240–247
Abstract: ... mitogen-activated protein kinase signals found increased phosphorylation of c-Jun terminal kinase (JNK) and higher activation ...
| Abstract | Temozolomide (TMZ) is one of the few effective anticancer agents against gliomas. However, acquisition of TMZ resistance or adaptation by gliomas is currently a crucial problem, especially increased invasiveness which is critical for the determination of clinical prognosis. This study investigated the molecular regulatory mechanisms of TMZ resistance in gliomas involved in invasiveness, particularly invadopodia formation, a molecular complex formed at the invasive front to cause extracellular matrix degradation during cellular local invasion. The TMZ-resistant clone of the U343 MG human glioma cell line (U343-R cells) was established. U343-R cells demonstrated higher invadopodia formation compared with U343 cells without TMZ resistance (U343-Con cells). Immunoblot analysis of DNA damage-related mitogen-activated protein kinase signals found increased phosphorylation of c-Jun terminal kinase (JNK) and higher activation of its downstream signaling in U343-R cells compared with U343-Con cells. Treatment of U343-R cells with specific inhibitors of JNK or siRNA targeting JNK suppressed up-regulation of invadopodia formation. In addition, paxillin, one of the known JNK effectors which is phosphorylated and affects cell migration, was phosphorylated at serine 178 in JNK activity-dependent manner. Expression of paxillin with mutation of the serine 178 phosphorylation site in U343-R cells blocked invadopodia formation. The present findings suggest that increased formation of invadopodia in U343-R cells is mediated by hyperactivation of JNK-paxillin signaling, and both JNK and paxillin might become targets of novel therapies against TMZ-resistant gliomas. |
|---|---|
| MeSH term(s) | Antineoplastic Agents, Alkylating/pharmacology ; Cell Line, Tumor ; Cell Movement/drug effects ; Dacarbazine/analogs & derivatives ; Dacarbazine/pharmacology ; Drug Resistance, Neoplasm ; Glioma/drug therapy ; Glioma/metabolism ; Glioma/pathology ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; Paxillin/metabolism ; Phosphorylation/drug effects ; Podosomes/drug effects ; Podosomes/metabolism ; Podosomes/pathology ; Signal Transduction/drug effects |
| Chemical Substances | Antineoplastic Agents, Alkylating ; Paxillin ; Dacarbazine (7GR28W0FJI) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; temozolomide (YF1K15M17Y) |
| Language | English |
| Publishing date | 2015-12 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 205723-2 |
| ISSN | 1090-2104 ; 0006-291X ; 0006-291X |
| ISSN (online) | 1090-2104 ; 0006-291X |
| ISSN | 0006-291X |
| DOI | 10.1016/j.bbrc.2015.10.122 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 116: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.