Abstract
Wnt reception at the membrane is complex and not fully understood. CD44 is a major Wnt target gene in the intestine and is essential for Wnt-induced tumor progression in colorectal cancer. Here we show that CD44 acts as a positive regulator of the Wnt receptor complex. Downregulation of CD44 expression decreases, whereas CD44 overexpression increases Wnt activity in a concentration-dependent manner. Epistasis experiments place CD44 function at the level of the Wnt receptor LRP6. Mechanistically, CD44 physically associates with LRP6 upon Wnt treatment and modulates LRP6 membrane localization. Moreover, CD44 regulates Wnt signaling in the developing brain of Xenopus laevis embryos as shown by a decreased expression of Wnt targets tcf-4 and en-2 in CD44 morphants.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Animals
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Cell Line, Tumor
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Cytoskeletal Proteins / antagonists & inhibitors
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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HEK293 Cells
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HeLa Cells
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Humans
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Hyaluronan Receptors / chemistry
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Hyaluronan Receptors / genetics
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Hyaluronan Receptors / metabolism*
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Hyaluronic Acid / chemistry
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Hyaluronic Acid / metabolism
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Low Density Lipoprotein Receptor-Related Protein-6 / metabolism*
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Oocytes / metabolism
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Protein Binding
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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RNA Interference
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RNA, Small Interfering / metabolism
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Wnt Proteins / metabolism
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Wnt Signaling Pathway*
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Xenopus laevis / growth & development
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Xenopus laevis / metabolism
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beta Catenin / metabolism
Substances
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Actins
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Cytoskeletal Proteins
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Hyaluronan Receptors
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LRP6 protein, human
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Low Density Lipoprotein Receptor-Related Protein-6
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Protein Isoforms
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RNA, Small Interfering
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Wnt Proteins
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beta Catenin
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ezrin
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Hyaluronic Acid