Abstract
Recent findings suggest that nuclear IGF1R binds to enhancer regions and functions as a transcriptional cofactor. However, the downstream transcriptional regulators of this pathway remain to be defined. Here, we show that nuclear IGF1R associates with the transcription factor LEF1 and increases promoter activity of LEF1 downstream target genes cyclin D1 and axin2. Furthermore, nuclear IGF1R augments protein levels of cyclin D1 and axin2. Our findings suggest a novel function for IGF1R, thus further emphasizing the important role of this receptor in cancer biology.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Axin Protein / genetics
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Axin Protein / metabolism
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Cell Line
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Cell Nucleus / metabolism
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Gene Expression Regulation
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Humans
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Insulin Receptor Substrate Proteins / metabolism
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Lymphoid Enhancer-Binding Factor 1 / metabolism*
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Promoter Regions, Genetic
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Protein Binding
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Protein Transport
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Receptor, IGF Type 1 / genetics
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Receptor, IGF Type 1 / metabolism*
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Transcriptional Activation / physiology*
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beta Catenin / metabolism
Substances
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Axin Protein
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Insulin Receptor Substrate Proteins
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Lymphoid Enhancer-Binding Factor 1
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Receptors, Cytoplasmic and Nuclear
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beta Catenin
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Cyclin D1
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Receptor, IGF Type 1