EPHA4 is overexpressed but not functionally active in Sezary syndrome

L Hameetman, L. van der Fits, W.H. Zoutman, J.J. Out-Luiting, G. Siegal, I.J.P. de Esch, M.H. Vermeer, C.P. Tensen

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

EPHA4 belongs to the largest subfamily of receptor tyrosine kinases. In addition to its function during development, overexpression of EPHA4 in tumors has been correlated with increased proliferation, migration and poor survival. Several genomewide transcription profiling studies have demonstrated high EPHA4 expression in Sézary syndrome (SS), a leukemic variant of cutaneous CD4+ T-cell lymphoma (CTCL) with an aggressive clinical course and poor prognosis. In this study we set out to explore the functional role of EPHA4 in SS. Both high EPHA4 mRNA and protein expression was found in circulating SS-cells of patients compared to healthy CD4+ T-cells. However, using a phosphospecific EPHA4 antibody, phosphorylation of the EPHA4 kinase domain was not detected in either circulating or skin residing SS cells. Moreover, treatment with the phosphatase inhibitor pervanadate did not result in detectable phosphorylation of the EPHA4 kinase domain, in either SS cells or in healthy CD4+ T-cells. Thus, the results from our study confirm high EPHA4 expression in SS cells both on the mRNA and protein levels, making EPHA4 a good diagnostic marker. However, the overexpressed EPHA4 does not appear to be functionally active and its overexpression might be secondary to other oncogenic drivers in SS, like STAT3 and TWIST1.
Original languageEnglish
Pages (from-to)31868-31876
JournalOncotarget
Volume6
Issue number31
DOIs
Publication statusPublished - 2015

Fingerprint

Sezary Syndrome
Phosphotransferases
Phosphorylation
Phospho-Specific Antibodies
T-Lymphocytes
Cutaneous T-Cell Lymphoma
Messenger RNA
Receptor Protein-Tyrosine Kinases
Phosphoric Monoester Hydrolases
Proteins
Skin
Survival

Cite this

Hameetman, L., van der Fits, L., Zoutman, W. H., Out-Luiting, J. J., Siegal, G., de Esch, I. J. P., ... Tensen, C. P. (2015). EPHA4 is overexpressed but not functionally active in Sezary syndrome. Oncotarget, 6(31), 31868-31876. https://doi.org/10.18632/oncotarget.5573
Hameetman, L ; van der Fits, L. ; Zoutman, W.H. ; Out-Luiting, J.J. ; Siegal, G. ; de Esch, I.J.P. ; Vermeer, M.H. ; Tensen, C.P. / EPHA4 is overexpressed but not functionally active in Sezary syndrome. In: Oncotarget. 2015 ; Vol. 6, No. 31. pp. 31868-31876.
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abstract = "EPHA4 belongs to the largest subfamily of receptor tyrosine kinases. In addition to its function during development, overexpression of EPHA4 in tumors has been correlated with increased proliferation, migration and poor survival. Several genomewide transcription profiling studies have demonstrated high EPHA4 expression in S{\'e}zary syndrome (SS), a leukemic variant of cutaneous CD4+ T-cell lymphoma (CTCL) with an aggressive clinical course and poor prognosis. In this study we set out to explore the functional role of EPHA4 in SS. Both high EPHA4 mRNA and protein expression was found in circulating SS-cells of patients compared to healthy CD4+ T-cells. However, using a phosphospecific EPHA4 antibody, phosphorylation of the EPHA4 kinase domain was not detected in either circulating or skin residing SS cells. Moreover, treatment with the phosphatase inhibitor pervanadate did not result in detectable phosphorylation of the EPHA4 kinase domain, in either SS cells or in healthy CD4+ T-cells. Thus, the results from our study confirm high EPHA4 expression in SS cells both on the mRNA and protein levels, making EPHA4 a good diagnostic marker. However, the overexpressed EPHA4 does not appear to be functionally active and its overexpression might be secondary to other oncogenic drivers in SS, like STAT3 and TWIST1.",
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Hameetman, L, van der Fits, L, Zoutman, WH, Out-Luiting, JJ, Siegal, G, de Esch, IJP, Vermeer, MH & Tensen, CP 2015, 'EPHA4 is overexpressed but not functionally active in Sezary syndrome' Oncotarget, vol. 6, no. 31, pp. 31868-31876. https://doi.org/10.18632/oncotarget.5573

EPHA4 is overexpressed but not functionally active in Sezary syndrome. / Hameetman, L; van der Fits, L.; Zoutman, W.H.; Out-Luiting, J.J.; Siegal, G.; de Esch, I.J.P.; Vermeer, M.H.; Tensen, C.P.

In: Oncotarget, Vol. 6, No. 31, 2015, p. 31868-31876.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Hameetman, L

AU - van der Fits, L.

AU - Zoutman, W.H.

AU - Out-Luiting, J.J.

AU - Siegal, G.

AU - de Esch, I.J.P.

AU - Vermeer, M.H.

AU - Tensen, C.P.

PY - 2015

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AB - EPHA4 belongs to the largest subfamily of receptor tyrosine kinases. In addition to its function during development, overexpression of EPHA4 in tumors has been correlated with increased proliferation, migration and poor survival. Several genomewide transcription profiling studies have demonstrated high EPHA4 expression in Sézary syndrome (SS), a leukemic variant of cutaneous CD4+ T-cell lymphoma (CTCL) with an aggressive clinical course and poor prognosis. In this study we set out to explore the functional role of EPHA4 in SS. Both high EPHA4 mRNA and protein expression was found in circulating SS-cells of patients compared to healthy CD4+ T-cells. However, using a phosphospecific EPHA4 antibody, phosphorylation of the EPHA4 kinase domain was not detected in either circulating or skin residing SS cells. Moreover, treatment with the phosphatase inhibitor pervanadate did not result in detectable phosphorylation of the EPHA4 kinase domain, in either SS cells or in healthy CD4+ T-cells. Thus, the results from our study confirm high EPHA4 expression in SS cells both on the mRNA and protein levels, making EPHA4 a good diagnostic marker. However, the overexpressed EPHA4 does not appear to be functionally active and its overexpression might be secondary to other oncogenic drivers in SS, like STAT3 and TWIST1.

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DO - 10.18632/oncotarget.5573

M3 - Article

VL - 6

SP - 31868

EP - 31876

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 31

ER -

Hameetman L, van der Fits L, Zoutman WH, Out-Luiting JJ, Siegal G, de Esch IJP et al. EPHA4 is overexpressed but not functionally active in Sezary syndrome. Oncotarget. 2015;6(31):31868-31876. https://doi.org/10.18632/oncotarget.5573