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Erythropoietin drives breast cancer progression by activation of its receptor EPOR
Chan, K.K. Matchett, K.B. Coulter, J.A. Yuen, H-F. McCrudden, C.M. Zhang, S-D. Irwin, G.W. Davidson, M.A. Rülicke, T. Schober, S.
Chan, K.K.
Matchett, K.B.
Coulter, J.A.
Yuen, H-F.
McCrudden, C.M.
Zhang, S-D.
Irwin, G.W.
Davidson, M.A.
Rülicke, T.
Schober, S.
Publication Date
2017-03-18
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© 2017 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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openAccess
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2017-02-27
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Abstract
Breast cancer is a leading cause of cancer-related deaths. Anemia is common in
breast cancer patients and can be treated with blood transfusions or with recombinant
erythropoietin (EPO) to stimulate red blood cell production. Clinical studies have
indicated decreased survival in some groups of cancer patients treated with EPO.
Numerous tumor cells express the EPO receptor (EPOR), posing a risk that EPO
treatment would enhance tumor growth, but the mechanisms involved in breast tumor
progression are poorly understood.
Here, we have examined the functional role of the EPO-EPOR axis in preclinical
models of breast cancer. EPO induced the activation of PI3K/AKT and MAPK
pathways in human breast cancer cell lines. EPOR knockdown abrogated human
tumor cell growth, induced apoptosis through Bim, reduced invasiveness, and caused
downregulation of MYC expression. EPO-induced MYC expression is mediated through
the PI3K/AKT and MAPK pathways, and overexpression of MYC partially rescued loss
of cell proliferation caused by EPOR downregulation. In a xenotransplantation model,
designed to simulate recombinant EPO therapy in breast cancer patients, knockdown
of EPOR markedly reduced tumor growth.
Thus, our experiments in vitro and in vivo demonstrate that functional EPOR
signaling is essential for the tumor-promoting effects of EPO and underline the
importance of the EPO-EPOR axis in breast tumor progression.
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Citation
Chan KK, Matchett KB, Coulter JA et al (2017) Erythropoietin drives breast cancer progression by activation of its receptor EPOR. Oncotarget. 8(24): 38251-38263.
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