Activation of FGFR1β signaling pathway promotes survival, migration and resistance to chemotherapy in acute myeloid leukemia cells
Fibroblast growth factors (FGFs) are important regulators of hematopoiesis and have been implicated in the tumorigenesis of solid tumors. Recent evidence suggests that FGF signaling through FGF receptors (FGFRs) may play a role in the proliferation of subsets of acute myeloid leukemias (AMLs). Howev...
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| Veröffentlicht in: | Leukemia 2006-06, Vol.20 (6), p.979-986 |
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| creator | KARAJANNIS, M. A VINCENT, L RAFII, S DIRENZO, R SHMELKOV, S. V ZHANG, F FELDMAN, E. J BOHLEN, P ZHU, Z SUN, H KUSSIE, P |
| description | Fibroblast growth factors (FGFs) are important regulators of hematopoiesis and have been implicated in the tumorigenesis of solid tumors. Recent evidence suggests that FGF signaling through FGF receptors (FGFRs) may play a role in the proliferation of subsets of acute myeloid leukemias (AMLs). However, the precise mechanism and specific FGF receptors that support leukemic cell growth are not known. We show that FGF-2, through activation of FGFR1β signaling, promotes survival, proliferation and migration of AML cells. Stimulation of FGFR1β results in phosphoinositide 3-kinase (PI3-K)/Akt activation and inhibits chemotherapy-induced apoptosis of leukemic cells. Neutralizing FGFR1-specific antibody abrogates the physiologic and chemoprotective effects of FGF-2/FGFR1β signaling and inhibits tumor growth in mice xenotransplanted with human AML. These data suggest that activation of FGF-2/FGFR1β supports progression and chemoresistance in subsets of AML. Therefore, FGFR1 targeting may be of therapeutic benefit in subsets of AML. |
| doi_str_mv | 10.1038/sj.leu.2404203 |
| format | Article |
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A ; VINCENT, L ; RAFII, S ; DIRENZO, R ; SHMELKOV, S. V ; ZHANG, F ; FELDMAN, E. J ; BOHLEN, P ; ZHU, Z ; SUN, H ; KUSSIE, P</creator><creatorcontrib>KARAJANNIS, M. A ; VINCENT, L ; RAFII, S ; DIRENZO, R ; SHMELKOV, S. V ; ZHANG, F ; FELDMAN, E. J ; BOHLEN, P ; ZHU, Z ; SUN, H ; KUSSIE, P</creatorcontrib><description>Fibroblast growth factors (FGFs) are important regulators of hematopoiesis and have been implicated in the tumorigenesis of solid tumors. Recent evidence suggests that FGF signaling through FGF receptors (FGFRs) may play a role in the proliferation of subsets of acute myeloid leukemias (AMLs). However, the precise mechanism and specific FGF receptors that support leukemic cell growth are not known. We show that FGF-2, through activation of FGFR1β signaling, promotes survival, proliferation and migration of AML cells. Stimulation of FGFR1β results in phosphoinositide 3-kinase (PI3-K)/Akt activation and inhibits chemotherapy-induced apoptosis of leukemic cells. Neutralizing FGFR1-specific antibody abrogates the physiologic and chemoprotective effects of FGF-2/FGFR1β signaling and inhibits tumor growth in mice xenotransplanted with human AML. These data suggest that activation of FGF-2/FGFR1β supports progression and chemoresistance in subsets of AML. Therefore, FGFR1 targeting may be of therapeutic benefit in subsets of AML.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2404203</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>1-Phosphatidylinositol 3-kinase ; Acute myeloid leukemia ; AKT protein ; Antibodies ; Apoptosis ; Biological and medical sciences ; Cell migration ; Cell proliferation ; Chemoresistance ; Chemotherapy ; Fibroblast growth factor 2 ; Fibroblast growth factor receptor 1 ; Growth factors ; Hematologic and hematopoietic diseases ; Hematopoiesis ; Kinases ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences ; Receptors ; Signal transduction ; Signaling ; Solid tumors ; Survival ; Tumorigenesis ; Tumors ; Xenografts</subject><ispartof>Leukemia, 2006-06, Vol.20 (6), p.979-986</ispartof><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Nature Publishing Group 2006.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-9b3b13c4321f264fe5d10f366889cac1cec5f0eca59b3196d86cd742f38de0953</citedby><cites>FETCH-LOGICAL-c407t-9b3b13c4321f264fe5d10f366889cac1cec5f0eca59b3196d86cd742f38de0953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17821046$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>KARAJANNIS, M. 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However, the precise mechanism and specific FGF receptors that support leukemic cell growth are not known. We show that FGF-2, through activation of FGFR1β signaling, promotes survival, proliferation and migration of AML cells. Stimulation of FGFR1β results in phosphoinositide 3-kinase (PI3-K)/Akt activation and inhibits chemotherapy-induced apoptosis of leukemic cells. Neutralizing FGFR1-specific antibody abrogates the physiologic and chemoprotective effects of FGF-2/FGFR1β signaling and inhibits tumor growth in mice xenotransplanted with human AML. These data suggest that activation of FGF-2/FGFR1β supports progression and chemoresistance in subsets of AML. Therefore, FGFR1 targeting may be of therapeutic benefit in subsets of AML.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Acute myeloid leukemia</subject><subject>AKT protein</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Fibroblast growth factor 2</subject><subject>Fibroblast growth factor receptor 1</subject><subject>Growth factors</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematopoiesis</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical sciences</subject><subject>Receptors</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Solid tumors</subject><subject>Survival</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpVkUGLFDEQhYMoOK5ePQdET_aYdDrp9HFYnFVYEETPTTZdmc6Y7oyp9Mqc_Uf-kP1Nm2EG1FOg8r3Hq1eEvOZszZnQH3C_DrCs64Y1NRNPyIo3raqklPwpWTGt20p1dfOcvEDcM3b6VCvye2OzvzfZx5lGR7c326_84Q9Fv5tN8POOHkwef5kjPaQ4xQxIcUn3RRHe08nv0llp5oEmQI_ZzBZojtSOUPARkjkcqS-EXTLQ6Qgh-oGWnD9g8oZaCAFfkmfOBIRXl_eKfN9-_Hb9qbr9cvP5enNb2Ya1ueruxB0XthE1d7VqHMiBMyeU0rqzxnILVjoG1shC8k4NWtmhbWon9ACsk-KKvDn7ll1-LoC538cllT2xL36yZa2WrFDrM7UzAXo_u5iTKf5mKIltnMH5Mt9wraXgNT8J3v0jGMGEPGIMy6kZ_B-8ONsUERO4_pD8ZNKx56w_nbDHfV-q6S8nLIK3l8AGrQkulXY9_lW1utg2SjwCpweetQ</recordid><startdate>20060601</startdate><enddate>20060601</enddate><creator>KARAJANNIS, M. 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A</au><au>VINCENT, L</au><au>RAFII, S</au><au>DIRENZO, R</au><au>SHMELKOV, S. V</au><au>ZHANG, F</au><au>FELDMAN, E. J</au><au>BOHLEN, P</au><au>ZHU, Z</au><au>SUN, H</au><au>KUSSIE, P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of FGFR1β signaling pathway promotes survival, migration and resistance to chemotherapy in acute myeloid leukemia cells</atitle><jtitle>Leukemia</jtitle><date>2006-06-01</date><risdate>2006</risdate><volume>20</volume><issue>6</issue><spage>979</spage><epage>986</epage><pages>979-986</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>Fibroblast growth factors (FGFs) are important regulators of hematopoiesis and have been implicated in the tumorigenesis of solid tumors. Recent evidence suggests that FGF signaling through FGF receptors (FGFRs) may play a role in the proliferation of subsets of acute myeloid leukemias (AMLs). However, the precise mechanism and specific FGF receptors that support leukemic cell growth are not known. We show that FGF-2, through activation of FGFR1β signaling, promotes survival, proliferation and migration of AML cells. Stimulation of FGFR1β results in phosphoinositide 3-kinase (PI3-K)/Akt activation and inhibits chemotherapy-induced apoptosis of leukemic cells. Neutralizing FGFR1-specific antibody abrogates the physiologic and chemoprotective effects of FGF-2/FGFR1β signaling and inhibits tumor growth in mice xenotransplanted with human AML. These data suggest that activation of FGF-2/FGFR1β supports progression and chemoresistance in subsets of AML. Therefore, FGFR1 targeting may be of therapeutic benefit in subsets of AML.</abstract><cop>London</cop><pub>Nature Publishing</pub><doi>10.1038/sj.leu.2404203</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase Acute myeloid leukemia AKT protein Antibodies Apoptosis Biological and medical sciences Cell migration Cell proliferation Chemoresistance Chemotherapy Fibroblast growth factor 2 Fibroblast growth factor receptor 1 Growth factors Hematologic and hematopoietic diseases Hematopoiesis Kinases Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Receptors Signal transduction Signaling Solid tumors Survival Tumorigenesis Tumors Xenografts |
| title | Activation of FGFR1β signaling pathway promotes survival, migration and resistance to chemotherapy in acute myeloid leukemia cells |
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