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Sunitinib deregulates tumor adaptation to hypoxia by inhibiting HIF-1α synthesis in HT-29 colon cancer cells

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dc.contributor.authorShin, Hyun-Woo-
dc.contributor.authorCho, Chung-Hyun-
dc.contributor.authorKim, Tae-You-
dc.contributor.authorPark, Jong-Wan-
dc.date.accessioned2012-05-25T06:36:31Z-
dc.date.available2012-05-25T06:36:31Z-
dc.date.issued2010-07-23-
dc.identifier.citationBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS; Vol.398 2; 205-211ko_KR
dc.identifier.issn0006-291X-
dc.identifier.urihttps://hdl.handle.net/10371/76478-
dc.description.abstractSunitinib (SU11248, Sutent (R)) is a class III/V receptor tyrosine kinase (RTK) inhibitor that exhibits potent anti-angiogenic and anticancer activities. Preclinical studies demonstrated that the sunitinib effects are attributed to inhibition of VEGFR and PDGFR phosphorylation. However, even in colon cancer cells lacking sunitinib-targeted RTKs, sunitinib effectively inhibits tumor growth in a xenograft model, and this raises a question about the mechanism underlying the in vivo anticancer action of sunitinib. Since hypoxia is a critical microenvironment that tumors face, we addressed the possibility that sunitinib deregulates tumor adaptation to hypoxia. First we found that sunitinib limits the colony growth of HT-29, which is a colon adenocarcinoma cell line lacking the RTKs, and that HIF-1 alpha in the colonies is decreased by sunitinib. In cultured HT-29 cells, sunitinib suppressed HIF-1 alpha under hypoxic conditions. Moreover, sunitinib repressed the activity of HIF-1 alpha and subsequently decreased the expressions of HIF-1 downstream genes. Mechanistically, sunitinib blocked the 5`-UTR-dependent translation of HIF-1 alpha. The HIF-1 alpha suppression by sunitinib was also reproduced in a VHL-null renal cell carcinoma cell line, where HIF-1 alpha is not degradable. In conclusion, the sunitinib inhibition of HIF-1 signaling could restrain tumor progression in hypoxic regions, which may contribute to anticancer effect of sunitinib. (C) 2010 Elsevier Inc. All rights reserved.ko_KR
dc.language.isoenko_KR
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCEko_KR
dc.subjectSunitinibko_KR
dc.subjectTumor hypoxiako_KR
dc.subjectColony formationko_KR
dc.subjectProtein synthesisko_KR
dc.subjectHypoxia-inducible factor 1ko_KR
dc.titleSunitinib deregulates tumor adaptation to hypoxia by inhibiting HIF-1α synthesis in HT-29 colon cancer cellsko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor신현우-
dc.contributor.AlternativeAuthor조정현-
dc.contributor.AlternativeAuthor김태유-
dc.contributor.AlternativeAuthor박종완-
dc.identifier.doi10.1016/j.bbrc.2010.06.060-
dc.citation.journaltitleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS-
dc.description.citedreferenceSonpavde G, 2009, UROL ONCOL-SEMIN ORI, V27, P391, DOI 10.1016/j.urolonc.2008.03.017-
dc.description.citedreferenceKontovinis LF, 2009, BMC CANCER, V9, DOI 10.1186/1471-2407-9-82-
dc.description.citedreferenceCHO YS, 2009, MOL CELLS-
dc.description.citedreferenceBURKITT K, 2009, MOL CANC THER-
dc.description.citedreferenceBirk DM, 2008, VASC ENDOVASC SURG, V42, P517, DOI 10.1177/1538574408322755-
dc.description.citedreferenceRini BI, 2008, J CLIN ONCOL, V26, P3743, DOI 10.1200/JCO.2007.15.5416-
dc.description.citedreferenceChow LQM, 2007, J CLIN ONCOL, V25, P884, DOI 10.1200/JCO.2006.06.3602-
dc.description.citedreferenceMotzer RJ, 2007, NEW ENGL J MED, V356, P115-
dc.description.citedreferencePatel PH, 2006, CLIN CANCER RES, V12, P7215, DOI 10.1158/1078-0432.CCR-06-2254-
dc.description.citedreferenceDemetri GD, 2006, LANCET, V368, P1329, DOI 10.1016/S0140-6736(06)69446-4-
dc.description.citedreferencePotapova O, 2006, MOL CANCER THER, V5, P1280, DOI 10.1158/1535-7163.MCT-03-0156-
dc.description.citedreferenceYeo EJ, 2006, BLOOD, V107, P916, DOI 10.1182/blood-2005-06-2564-
dc.description.citedreferenceChen WT, 2005, JPN J CLIN ONCOL, V35, P207, DOI 10.1093/jjco/hyi067-
dc.description.citedreferenceGINGERICH TJ, 2004, ANIM HEALTH RES REV, V5, P49, DOI 10.1079/AHRR200460-
dc.description.citedreferenceTakahashi R, 2003, ONCOL REP, V10, P797-
dc.description.citedreferenceYeo EJ, 2003, J NATL CANCER I, V95, P516-
dc.description.citedreferenceMendel DB, 2003, CLIN CANCER RES, V9, P327-
dc.description.citedreferenceHudson CC, 2002, MOL CELL BIOL, V22, P7004, DOI 10.1128/MCB.22.20.7004-7014.2002-
dc.description.citedreferenceLang KJD, 2002, MOL BIOL CELL, V13, P1792, DOI 10.1091/mbc.02-02-0017-
dc.description.citedreferenceArsham AM, 2002, J BIOL CHEM, V277, P15162, DOI 10.1074/jbc.M111162200-
dc.description.citedreferenceLaughner E, 2001, MOL CELL BIOL, V21, P3995-
dc.description.citedreferenceYamashita K, 2001, J BIOL CHEM, V276, P12645-
dc.description.citedreferenceHockel M, 2001, J NATL CANCER I, V93, P266-
dc.description.citedreferenceTanimoto K, 2000, EMBO J, V19, P4298-
dc.description.citedreferenceTalks KL, 2000, AM J PATHOL, V157, P411-
dc.description.citedreferenceChun YS, 2000, BIOCHEM BIOPH RES CO, V268, P652-
dc.description.citedreferenceTAKAHASHI Y, 1995, CANCER RES, V55, P3964-
dc.description.citedreferenceWANG GL, 1995, P NATL ACAD SCI USA, V92, P5510-
dc.description.tc4-
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