Received for publication August 9, 2007.
Revised December 11, 2007.
Accepted for publication December 11, 2007.

Erythropoietin stimulates cancer cell migration and activates RhoA protein through a MAPK/Erk-dependent mechanism

Abstract

Erythropoietin receptor (EpoR) is expressed in several cancer cell lines and the functional consequence of this expression is under extensive study. Here we use a cervical cancer cell line in which EpoR was first found to be expressed and to correlate with the severity of the disease. We demonstrate that Epo is a chemoattractant for these cancer cells enhancing their migration under serum starved conditions. Using a transwell migration system we show that Epo enhances cancer cell migration in a dose and time dependent manner. The effect of Epo is dependent on the activity of two signaling pathways: the MAP kinase and the RhoA GTPase pathways. We show that Epo activates both pathways in a Jak-dependent manner and that this activation is required for Epo effects on cell migration. Furthermore, we use both pharmacological and genetic inhibitors to demonstrate that the activation of RhoA GTPase is dependent on the activity of the MAP kinase pathway providing the first evidence for interaction between these two signaling cascades.

Key words: Erk, Erythropoietin, MAPK, RhoA, cancer, migration