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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
35
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pubmed:dateCreated |
2009-8-24
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pubmed:abstractText |
Recent molecular studies indicate that aerobic glycolysis plays an important role in tumorigenesis and is a valid target for cancer therapy. Although 2-deoxyglucose (2-DG) is well characterized as a glycolytic inhibitor, we recently discovered that it activates a prosurvival oncoprotein, AKT, through PI3K. In this study, we discovered that 2-DG treatments disrupted the binding between insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP3) so that the free form of IGF-1 could be released from the IGF-1.IGFBP3 complex to activate IGF-1 receptor (IGF1R) signaling. Because IGF1R signaling is involved, PI3K/AKT constitutes only one of the prosurvival pathways that are activated by 2-DG treatment; we validated that MEK-ERK signaling was also induced in an IGF1R-dependent manner in some cancer cell lines. Furthermore, our phospho-specific antibody microarray analysis indicated that 2-DG up-regulated the phosphorylation of 64 sites within various signaling pathways in H460 cells. Chemical inhibition of IGF1R reduced 57 of these up-regulations. These data suggest that 2-DG-induced activation of many survival pathways can be jointly attenuated through IGF1R inhibition. Our in vitro analysis demonstrated that treatment with a combination of subtoxic doses of 2-DG and the IGF1R inhibitor II reduced cancer cell proliferation 90% and promoted significant apoptosis.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-12094235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-12466191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-13298683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-14115684,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-14688466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-14729604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-15170449,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-15229476,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-15247904,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-15695406,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-16044218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-16111712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-16766262,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-16892078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-1727388,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-17496923,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-18337823,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-18413794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-18508432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-18794113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-18948947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-3893656,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-535913,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19574224-8641905
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:ChenJingJ,
pubmed-author:KhuriFadlo RFR,
pubmed-author:LiuTongruiT,
pubmed-author:LiuXiangguoX,
pubmed-author:LiuXiujuX,
pubmed-author:SunShi-YongSY,
pubmed-author:XiongLiL,
pubmed-author:ZhongDianshengD,
pubmed-author:ZhouQinghuaQ,
pubmed-author:ZhouWeiW,
pubmed-author:ZongYapingY
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pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
284
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23225-33
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:19574224-Cell Line, Tumor,
pubmed-meshheading:19574224-Cell Survival,
pubmed-meshheading:19574224-Deoxyglucose,
pubmed-meshheading:19574224-Glycolysis,
pubmed-meshheading:19574224-Humans,
pubmed-meshheading:19574224-Neoplasms,
pubmed-meshheading:19574224-Phosphorylation,
pubmed-meshheading:19574224-Receptor, IGF Type 1,
pubmed-meshheading:19574224-Signal Transduction
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pubmed:year |
2009
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pubmed:articleTitle |
The glycolytic inhibitor 2-deoxyglucose activates multiple prosurvival pathways through IGF1R.
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pubmed:affiliation |
Department of Hematology, Emory University, Atlanta, Georgia 30322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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