The EphA3 receptor is expressed in a subset of rhabdomyosarcoma cell lines and suppresses cell adhesion and migration.
Elevated expression of the Eph receptor tyrosine kinase EphA3 is associated with lymphocytic leukaemia, but little is known about its expression or function in solid tumours. Out of a panel of cancer cell lines, we found that EphA3 was expressed only on two rhabdomyosarcoma (RMS) cell lines of the embryonal histological subtype and on one of the alveolar RMS subtype, whereas it was not detected on two other cell lines of the alveolar subtype. Other EphA receptors (1-7) were, either not expressed in any, or expressed in all five RMS cell lines. Stimulation of EphA3-expressing TE671 and RD RMS cells with ephrinA5 resulted in loss of adhesion to fibronectin, decreased migration towards the stromal cell-derived growth factor-I (SDF-I), increased EphA3 phosphorylation, and increased Rho GTPase activity. In contrast, ectopic expression of EphA3 in the EphA3 negative CRL2061 cell line resulted in decreased cell adhesion. Finally, suppression of EphA3 expression by siRNA in RD cells results in increased SDF-I-mediated motility. These data indicate that EphA3 expression may define subsets of RMS tumours, and that EphA3 suppresses motility through regulation of Rho GTPases in RMS cells.
Clifford
Noretta
N
Cell Biology Laboratory, Department of Biochemistry, BioSciences Institute, University College Cork, Cork, Ireland.
Smith
Loraine M
LM
Powell
James
J
Gattenlöhner
Stefan
S
Marx
Alexander
A
O'Connor
Rosemary
R
D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D036386:Ephrin-A5 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D034741:RNA, Small Interfering / Q000378:metabolism; D036121:Receptor, EphA3 / Q000235:genetics / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D036386:Ephrin-A5; D034741:RNA, Small Interfering; D036121:Receptor, EphA3; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins