Erythropoietin stimulates cancer cell migration and activates RhoA protein through a mitogen-activated protein kinase/extracellular signal-regulated kinase-dependent mechanism

Sumaya N. Hamadmad, Raymond J. Hohl

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21 Citations (Scopus)

Abstract

Erythropoietin (Epo) receptor (EpoR) is expressed in several cancer cell lines, and the functional consequence of this expression is under extensive study. In this study, we used 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 mitogen-activated protein kinase (MAPK) pathway and the RhoA GTPase pathway. We show that Epo activates both pathways in a Janus kinase-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 MAPK pathway, providing the first evidence for interaction between these two signaling cascades.

Original languageEnglish (US)
Pages (from-to)1227-1233
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume324
Issue number3
DOIs
StatePublished - Mar 1 2008

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rhoA GTP-Binding Protein
Extracellular Signal-Regulated MAP Kinases
Erythropoietin
Mitogen-Activated Protein Kinases
Cell Movement
GTP Phosphohydrolases
Neoplasms
Erythropoietin Receptors
Janus Kinases
Cell Line
Chemotactic Factors
Uterine Cervical Neoplasms
Pharmacology
Serum

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

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title = "Erythropoietin stimulates cancer cell migration and activates RhoA protein through a mitogen-activated protein kinase/extracellular signal-regulated kinase-dependent mechanism",
abstract = "Erythropoietin (Epo) receptor (EpoR) is expressed in several cancer cell lines, and the functional consequence of this expression is under extensive study. In this study, we used 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 mitogen-activated protein kinase (MAPK) pathway and the RhoA GTPase pathway. We show that Epo activates both pathways in a Janus kinase-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 MAPK pathway, providing the first evidence for interaction between these two signaling cascades.",
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T1 - Erythropoietin stimulates cancer cell migration and activates RhoA protein through a mitogen-activated protein kinase/extracellular signal-regulated kinase-dependent mechanism

AU - Hamadmad, Sumaya N.

AU - Hohl, Raymond J.

PY - 2008/3/1

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N2 - Erythropoietin (Epo) receptor (EpoR) is expressed in several cancer cell lines, and the functional consequence of this expression is under extensive study. In this study, we used 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 mitogen-activated protein kinase (MAPK) pathway and the RhoA GTPase pathway. We show that Epo activates both pathways in a Janus kinase-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 MAPK pathway, providing the first evidence for interaction between these two signaling cascades.

AB - Erythropoietin (Epo) receptor (EpoR) is expressed in several cancer cell lines, and the functional consequence of this expression is under extensive study. In this study, we used 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 mitogen-activated protein kinase (MAPK) pathway and the RhoA GTPase pathway. We show that Epo activates both pathways in a Janus kinase-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 MAPK pathway, providing the first evidence for interaction between these two signaling cascades.

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