ArticleThe Journal of biological chemistry2012
Both LRP5 and LRP6 receptors are required to respond to physiological Wnt ligands in mammary epithelial cells and fibroblasts.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 75 citations in OpenAlex.
- LRP5 promotes adipose progenitor cell fitness and adipocyte insulin sensitivity.Communications medicine · 2025Article
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- Extraction of redox extracellular vesicles using exclusion-based sample preparation.Analytical and bioanalytical chemistry · 2024Article
- Utility of Wnt family member 9b (Wnt9b) immunohistochemistry in the cytologic diagnosis of metastatic breast carcinoma.Virchows Archiv : an international journal of pathology · 2024Article
- Knockdown of LRP5 Promotes Proliferation and Invasion of Tongue Squamous Cell Carcinoma through Compensatory Activation of Akt Signaling.Journal of Cancer · 2024Article
- Screening and Identification of ssDNA Aptamers for Low-Density Lipoprotein (LDL) Receptor-Related Protein 6.Molecules (Basel, Switzerland) · 2023Article
- Improving wastewater-based epidemiology performance through streamlined automation.Journal of environmental chemical engineering · 2023Article
- A role for β-catenin in diet-induced skeletal muscle insulin resistance.Physiological reports · 2023Article
- The role of WNT10B in physiology and disease: A 10-year update.Frontiers in cell and developmental biology · 2023Review
- The alteration of N6-methyladenosine (m6A) modification at the transcriptome-wide level in response of heat stress in bovine mammary epithelial cells.BMC genomics · 2022Article
- Disruption of β-Catenin-Dependent Wnt Signaling in Colon Cancer Cells Remodels the Microenvironment to Promote Tumor Invasion.Molecular cancer research : MCR · 2022Article
- Competitive blocking of LRP4-sclerostin binding interface strongly promotes bone anabolic functions.Cellular and molecular life sciences : CMLS · 2022Article
- Role of microRNA/lncRNA Intertwined With the Wnt/β-Catenin Axis in Regulating the Pathogenesis of Triple-Negative Breast Cancer.Frontiers in pharmacology · 2022Review
- miR-424/503 modulates Wnt/β-catenin signaling in the mammary epithelium by targeting LRP6.EMBO reports · 2021Article
- Mitotic WNT signalling orchestrates neurogenesis in the developing neocortex.The EMBO journal · 2021Article
- Distinct roles of LRP5 and LRP6 in Wnt signaling regulation in the retina.Biochemical and biophysical research communications · 2021Article
- LRP6 mediated signal transduction pathway triggered by tissue plasminogen activator acts through lipid rafts in neuroblastoma cells.Journal of cell communication and signaling · 2020Article
- Low-density lipoprotein receptor-related protein 6-mediated signaling pathways and associated cardiovascular diseases: diagnostic and therapeutic opportunities.Human genetics · 2020Review
- C-X-C motif chemokine receptor 4 aggravates renal fibrosis through activating JAK/STAT/GSK3β/β-catenin pathway.Journal of cellular and molecular medicine · 2020Article
- Attenuation of Wnt/β-catenin signaling in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.International journal of biological sciences · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A canonical Wnt signal maintains adult mammary ductal stem cell activity, and this signal requires the Wnt signaling reception, LRP5. However, previous data from our laboratory have shown that LRP5 and LRP6 are co-expressed in mammary basal cells and that LRP6 is active, leading us to question why LRP6 is insufficient to mediate canonical signaling in the absence of LRP5. Here, we show that at endogenous levels of LRP5 and LRP6 both receptors are required to signal in response to some Wnt ligands both in vitro (in mouse embryonic fibroblasts and mammary epithelial cells) and in vivo (in mammary outgrowths). This subgroup of canonical ligands includes Wnt1, Wnt9b, and Wnt10b; the latter two are expressed in mammary gland. In contrast, the ligand commonly used experimentally, Wnt3a, prefers LRP6 and requires just one receptor regardless of cellular context. When either LRP5 or LRP6 is overexpressed, signaling remains ligand-dependent, but the requirement for both receptors is abrogated (regardless of ligand type). We have documented an LRP5-6 heteromer using immiscible filtration assisted by surface tension (IFAST) immunoprecipitation. Together, our data imply that under physiological conditions some Wnt ligands require both receptors to be present to generate a canonical signal. We have designed a model to explain our results based on the resistance of LRP5-6 heteromers to a selective inhibitor of E1/2-binding Wnt-LRP6 interaction. These data have implications for stem cell biology and for the analysis of the oncogenicity of LRP receptors that are often overexpressed in breast tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.