التفاصيل البيبلوغرافية
| العنوان: |
Effect of v-Src on cell motility : speed, directionality and signalling pathways |
| المؤلفون: |
PÅ‚atek, Anna |
| المساهمون: |
UCL - MD/BICL/CELL - Unité de biologie cellulaire, Courtoy, Pierre Jacques |
| بيانات النشر: |
UCL |
| سنة النشر: |
2005 |
| المجموعة: |
DIAL@UCL (Université catholique de Louvain) |
| مصطلحات موضوعية: |
Cell Migration Inhibition, Sarcoma, Avian |
| الوصف: |
Cell motility, a key parameter in cancer invasion and metastasis, is driven by the actin cytoskeleton and can be oriented by extracellular signals. We have examined the role of oncogenic v-Src in spontaneous and oriented motility. The study was performed using Rat-1/tsLA29 and MDCK/tsLA31 cells, each harbouring a different thermosensitive v-Src kinase, active at 34°C but inactivated at 40°C. v-Src activation induced transformation of both cell lines and accelerated their spontaneous motility by 2-3-fold, as evidenced by time-lapse recording in Dunn chambers and wound-healing assay. Inhibitors of PI 3-kinase, PLC and PLD selectively abrogated acceleration of motility by v-Src, suggesting that these enzymes mediate v-Src-induced spontaneous migration. We further analysed in Dunn chambers the chemotactic response to platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) gradients. Oncogenic v-Src decreased by 2-3-fold the surface pool at steady-state of PDGF-receptors on Rat-1 fibroblasts and of EGF-receptors on MDCK cells. At levels of receptors occupancy comparable to those of non-transformed cells, v-Src abrogated chemotaxis towards these growth factors (GFs). Thus, v-Src accelerates spontaneous motility but abrogates chemotaxis. In the second part of the study we addressed the question why v-Src decreases the surface pool of GF-receptors and causes the loss of the chemotactic response. Overnight v-Src activation resulted in ~3-fold decrease in PDGFRb mRNA (as measured by quantitative real-time PCR), and total protein (Western blotting). PDGFR signalling, assessed using anti-Y751 phosphopeptide antibodies corresponding to the docking site for PI3-K, was not detected at 40°C in the absence of PDGF and was strongly induced by its addition. At 34°C, Y751 phosphorylation was already detected in the absence of ligand and further increased upon PDGF-stimulation, indicating that PDGFR in v-Src-transformed cells still responds to its cognate ligand. At 40°C, in a PDGF gradient, immunolabelled ... |
| نوع الوثيقة: |
doctoral or postdoctoral thesis |
| اللغة: |
English |
| العلاقة: |
boreal:247951; https://hdl.handle.net/2078.1/247951Test |
| الإتاحة: |
https://hdl.handle.net/2078.1/247951Test |
| حقوق: |
info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: |
edsbas.A6868526 |
| قاعدة البيانات: |
BASE |
