Abstract
Atoh1 plays a crucial role in intestinal cell differentiation. We have demonstrated that its human homolog Hath1 protein is targeted by the Wnt-GSK3 axis, resulting in the proteasomal degradation in human colon cancer. However, the contribution of Hath1 degradation to the undifferentiated state of colon cancer remains unknown. In this study, we demonstrated that both constitutive expression of mutant Hath1 and stabilization of Hath1 protein by a GSK3 inhibitor in colon cancer cells increased the expression of MUC2 known as a representative function of differentiated goblet cells. This means that Hath1 protein degradation may be required for maintaining the undifferentiated state of colon cancers, and that GSK3 inhibitors have potential for use in cancer therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Cell Differentiation
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Cell Line, Tumor
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Colonic Neoplasms / pathology
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Colonic Neoplasms / physiopathology*
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Glycogen Synthase Kinase 3 / antagonists & inhibitors
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Glycogen Synthase Kinase 3 beta
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Humans
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Lithium Chloride / pharmacology
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Mucin-2
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Mucins / biosynthesis
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Proteasome Endopeptidase Complex / metabolism*
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RNA, Messenger / metabolism
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Transcription, Genetic
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Wnt Proteins / physiology*
Substances
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ATOH1 protein, human
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Basic Helix-Loop-Helix Transcription Factors
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MUC2 protein, human
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Mucin-2
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Mucins
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RNA, Messenger
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Wnt Proteins
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3
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Proteasome Endopeptidase Complex
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Lithium Chloride