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The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
TLDR
The beta-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells. Expand
The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength.
TLDR
The Lgr5/R-spondin complex acts by neutralizing Rnf43 and Znrf3, two transmembrane E3 ligases that remove Wnt receptors from the stem cell surface. Expand
Peyer's Patch M Cells Derived from Lgr5+ Stem Cells Require SpiB and Are Induced by RankL in Cultured “Miniguts”
TLDR
It is shown that in intestinal organoid (“minigut”) cultures, stimulation with RankL induces SpiB expression within 24 h and expression of other M cell markers subsequently, which concludes that RankL-induced expression of SpIB is essential for Lgr5 stem cell-derived epithelial precursors to develop into M cells. Expand
Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5.
TLDR
The data reveal binding of R-spondins to conserved sites on LGR4-LGR6 and, in analogy to FSHR and related receptors, suggest a direct signaling role for LGR 4-L GR6 in addition to its formation of Wnt receptor and coreceptor complexes. Expand
Monoclonal Antibodies Against Lgr5 Identify Human Colorectal Cancer Stem Cells
TLDR
Evidence is provided that Lgr5 is, next to a functional intestinal stem cell marker, a selective marker for human colorectal CSCs, and it is confirmed that L Gr5 expression is dependent on the Wnt pathway and show that L gr5 overexpression induces clonogenic growth. Expand
Phosphatidylinositol 3-Kinase Signaling Does Not Activate the Wnt Cascade
TLDR
It is shown that compartmentalization by Axin of GSK3 prohibits cross-talk between the PI3K and Wnt pathways and that Wnt-mediated transcriptional activity is not modulated by activation of thePI3K/PKB pathway. Expand
The R-spondin protein family
TLDR
Although R-spondins are unable to initiate Wnt signaling, they can potently enhance responses to low-dose Wnt proteins, and these findings might guide the therapeutic use of R- spondins in regenerative medicine. Expand
WNT signaling in the normal intestine and colorectal cancer.
TLDR
This review covers work from the past decade and highlights the importance of the canonical Wnt pathway in regulating multiple aspects of intestinal homeostasis, including transcriptional regulation of members of the Eph and Ephrin families. Expand
Structures of Wnt-Antagonist ZNRF3 and Its Complex with R-Spondin 1 and Implications for Signaling
TLDR
Crystal structures of the ZNRF3 ectodomain and its complex with R-spondin 1 (RSPO1) are presented and sequence conservation suggests a single ligand-binding site on ZNRf3, consistent with the proposed competing binding role of Z NRF3/RNF43 in Wnt signaling. Expand
Aberrantly expressed LGR4 empowers Wnt signaling in multiple myeloma by hijacking osteoblast-derived R-spondins
TLDR
A pivotal role is uncovered for the R-spondin/leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) axis in driving aberrant Wnt/β-catenin signaling in multiple myeloma cells. Expand
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