Mesd is a universal inhibitor of wnt coreceptors lrp5 and lrp6 and blocks wnt/β-catenin signaling in cancer cells

Wenyan Lu, Chia-Chen Liu, Jaideep V. Thottassery, Guojun D Bu, Yonghe Li

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Mesd is a specialized chaperone for low-density lipoprotein receptor-related protein 5 (LRP5) and LRP6. In our previous studies, we found that Mesd binds to mature LRP6 on the cell surface and blocks the binding of Wnt antagonist Dickkopf-1 (Dkk1) to LRP6. Herein, we demonstrate that Mesd also binds to LRP5 with a high affinity and is a universal inhibitor of LRP5 and LRP6 ligands. Mesd not only blocks binding of Wnt antagonists Dkk1 and Sclerostin to LRP5 and LRP6 but also inhibits Wnt3A and Rspondin1-induced Wnt/β-catenin signaling in LRP5-and LRP6-expressing cells. We also found that Mesd, Dkk1, and Sclerostin compete with one another for binding to LRP5 and LRP6 at the cell surface. More importantly, we demonstrated that Mesd is able to suppress LRP6 phosphorylation and Wnt/β-catenin signaling in prostate cancer PC-3 cells and inhibits PC-3 cell proliferation. Our results indicate that recombinant Mesd protein is a useful tool for studying Wnt/β-catenin signaling on the cell surface and has a potential therapeutic role in Wnt-dependent cancers.

Original languageEnglish (US)
Pages (from-to)4635-4643
Number of pages9
JournalBiochemistry
Volume49
Issue number22
DOIs
StatePublished - Jun 8 2010
Externally publishedYes

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Low Density Lipoprotein Receptor-Related Protein-5
Catenins
Cells
Neoplasms
Recombinant proteins
Phosphorylation
Cell proliferation
Recombinant Proteins
Prostatic Neoplasms
Cell Proliferation
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mesd is a universal inhibitor of wnt coreceptors lrp5 and lrp6 and blocks wnt/β-catenin signaling in cancer cells. / Lu, Wenyan; Liu, Chia-Chen; Thottassery, Jaideep V.; Bu, Guojun D; Li, Yonghe.

In: Biochemistry, Vol. 49, No. 22, 08.06.2010, p. 4635-4643.

Research output: Contribution to journalArticle

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