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      Erythropoietin Stimulates Tumor Growth via EphB4.

      1 , 1 , 2 , 1 , 3 , 1 , 1 , 4 ,   1 , 5 , 5 , 1 , 6 , 1 , 1 , 1 , 1 , 7 , 8 , 1 , 8 , 1 , 9 , 9 , 10 , 10 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 10 , 11 , 11 , 1 , 1 , 12 , 1 , 13 , 9 , 14 , 15 , 5 , 16

      Cancer cell

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          Abstract

          While recombinant human erythropoietin (rhEpo) has been widely used to treat anemia in cancer patients, concerns about its adverse effects on patient survival have emerged. A lack of correlation between expression of the canonical EpoR and rhEpo's effects on cancer cells prompted us to consider the existence of an alternative Epo receptor. Here, we identified EphB4 as an Epo receptor that triggers downstream signaling via STAT3 and promotes rhEpo-induced tumor growth and progression. In human ovarian and breast cancer samples, expression of EphB4 rather than the canonical EpoR correlated with decreased disease-specific survival in rhEpo-treated patients. These results identify EphB4 as a critical mediator of erythropoietin-induced tumor progression and further provide clinically significant dimension to the biology of erythropoietin.

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          Author and article information

          Journal
          Cancer Cell
          Cancer cell
          1878-3686
          1535-6108
          Nov 9 2015
          : 28
          : 5
          Affiliations
          [1 ] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77584, USA.
          [2 ] Department of Surgery, University of Puerto Rico, San Juan 00936, Puerto Rico; University of Puerto Rico Comprehensive Cancer Center, San Juan 00936, Puerto Rico; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77584, USA.
          [3 ] Department of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX 77584, USA.
          [4 ] Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC 27599, USA.
          [5 ] Molecular Health, GmbH, Heidelberg 69115, Germany.
          [6 ] Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
          [7 ] Department of Surgery, University of Puerto Rico, San Juan 00936, Puerto Rico.
          [8 ] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77584, USA; Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
          [9 ] Department of Biochemistry and Molecular Biology and Center for Biomolecular Structure and Function, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
          [10 ] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
          [11 ] Molecular Neurology, Sygnis AG, Heidelberg 69120, Germany.
          [12 ] Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung 402, Taiwan.
          [13 ] Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
          [14 ] Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
          [15 ] Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
          [16 ] Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77584, USA; Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org.
          Article
          S1535-6108(15)00339-6 NIHMS725533
          10.1016/j.ccell.2015.09.008
          26481148
          Copyright © 2015 Elsevier Inc. All rights reserved.

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