Receptor EphA2 activation with ephrinA1 suppresses growth of malignant mesothelioma (MM).
The objective of this study was to understand the possible mechanisms of activation of receptor EphA2 by its ligand ephrinA1 in malignant mesothelioma cell (MMC) growth. Activation of receptor EphA2 by its ligand ephrinA1 triggered the phosphorylation of EphA2. Ligand activation of EphA2 also induced phosphorylation of ERK1/2 and significantly decreased MMC proliferation. Ligand activated and ephrinA1 vector (pcDNA/EFNA1) transfected MMC demonstrated decreased clonal growth in 3-D matrigels when compared to resting MMC. These studies suggest that EphA2 activation by its ligand ephrinA1 transmits intracellular signals from cell membrane to nucleus via ERK1/2 signaling cascade and inhibits MM growth.
Nasreen
Najmunnisa
N
Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Florida, P.O. Box 100225, Gainesville, FL, USA.
Mohammed
Kamal A
KA
Lai
Yimu
Y
Antony
Veena B
VB
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D036382:Ephrin-A1 / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D036104:Receptor, EphA2 / Q000378:metabolism*; D014162:Transfection
D036382:Ephrin-A1; D036104:Receptor, EphA2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3