Cancer Letters
Volume 258, Issue 2 , Pages 215-222, 18 December 2007

Receptor EphA2 activation with ephrinA1 suppresses growth of malignant mesothelioma (MM)☆

Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Florida, P.O. Box 100225, Gainesville, FL, USA

Received 26 June 2007; received in revised form 6 September 2007; accepted 10 September 2007. published online 18 October 2007.

Abstract 

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.

Keywords: EphA2, EphrinA1, Malignant mesothelioma, Receptor tyrosine kinase, Proliferation, ERK1/2

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☆ This work was supported by NIH RO1 AI 45338-02 grant from the National Institute of Health.

PII: S0304-3835(07)00425-9

doi:10.1016/j.canlet.2007.09.005

Cancer Letters
Volume 258, Issue 2 , Pages 215-222, 18 December 2007

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