ArticleCarcinogenesis2014
LGR5 positivity defines stem-like cells in colorectal cancer.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 165 citations in OpenAlex.
- A core transcriptional regulatory circuitry controls super-enhancer-driven activation of LGR5 in colorectal cancer.Nature communications · 2026Article
- Review
- Identification of tumor initiating cells and early marker genes in histologically normal colonic mucosa that lead to neoplastic transformation.Neoplasia (New York, N.Y.) · 2026Article
- Single nuclei and spatial profiling of sacrococcygeal teratomas reveals cellular composition and X inactivation heterogeneity.NPJ precision oncology · 2026Article
- Comparison of sterilisation methods for deer velvet antler extracts and their impact on anticancer activity.Frontiers in pharmacology · 2026Article
- Identification of tumor initiating cells and early marker genes in normal colonic epithelium that lead to neoplastic transformation.Research square · 2025Article
- Cetuximab increases LGR5 expression and augments LGR5-targeting antibody-drug conjugate efficacy in patient-derived colorectal cancer models.Cell reports. Medicine · 2025Article
- Review
- CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges.Nature reviews. Gastroenterology & hepatology · 2025Review
- Cetuximab increases LGR5 expression and augments LGR5-targeting antibody-drug conjugate efficacy in patient-derived colorectal cancer models.bioRxiv : the preprint server for biology · 2025Article
- Article
- ONC201 exerts oncogenic effects beyond its mitochondria-disturbing role in neuroblastoma subsets.Journal of molecular medicine (Berlin, Germany) · 2025Article
- LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance.Cancer metastasis reviews · 2025Review
- Article
- Nanomaterial-based detection of circulating tumor cells and circulating cancer stem cells for cancer immunotherapy.Nano convergence · 2024Review
- Article
- Exploring LGR5 as a prognostic marker of extrahepatic cholangiocarcinoma: insights from expression analysis and clinical correlations.Diagnostic pathology · 2024Article
- Article
- G protein-coupled receptor-targeting antibody-drug conjugates: Current status and future directions.Cancer letters · 2023Review
- Stiffness Restricts the Stemness of the Intestinal Stem Cells and Skews Their Differentiation Toward Goblet Cells.Gastroenterology · 2023Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 7 institutions in 4 countries.
Funding
Abstract
Like normal colorectal epithelium, colorectal carcinomas (CRCs) are organized hierarchically and include populations of cells with stem-like properties. Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) is associated with these stem cells in normal colorectal epithelium; however, the precise function of LGR5 in CRC remains largely unknown. Here, we analyzed the functional and molecular consequences of short hairpin RNA-mediated silencing of LGR5 in CRC cell lines SW480 and HT-29. Additionally, we exposed Lgr5-EGFP-IRES-CreERT2 mice to azoxymethane/dextrane sodium sulfate (AOM/DSS), which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were molecularly characterized using gene expression profiling and array comparative genomic hybridization. Silencing of LGR5 in SW480 CRC cells resulted in a depletion of spheres but did not affect adherently growing cells. Spheres expressed higher levels of several stem cell-associated genes than adherent cells, including LGR5. Silencing of LGR5 reduced proliferation, migration and colony formation in vitro and tumorigenicity in vivo. In accordance with these results, NOTCH signaling was downregulated upon LGR5 silencing. In AOM/DSS-induced colon tumors, Lgr5 high cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal colon cells. Array comparative genomic hybridization revealed no genomic imbalances in either tumor cell fraction. Our data elucidate mechanisms that define the role of LGR5 as a marker for stem-like cells in CRC.
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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.