ArticlePloS one2016
LGR5 Is a Gastric Cancer Stem Cell Marker Associated with Stemness and the EMT Signature Genes NANOG, NANOGP8, PRRX1, TWIST1, and BMI1.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
- PGD2/PTGDR2 Signaling Affects the Stemness of Gastric Cancer Stem Cells by Regulating Autophagy.Combinatorial chemistry & high throughput screening · 2026Article
- LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance.Cancer metastasis reviews · 2025Review
- Exploring LGR5 as a prognostic marker of extrahepatic cholangiocarcinoma: insights from expression analysis and clinical correlations.Diagnostic pathology · 2024Article
- NAT10-mediated acHeliyon · 2024Article
- Development of a Genetically Engineered Mouse Model Recapitulating LKB1 and PTEN Deficiency in Gastric Cancer Pathogenesis.Cancers · 2023Article
- Cancer stem cells: an insight into the development of metastatic tumors and therapy resistance.Stem cell reviews and reports · 2023Review
- Review
- The origin of gastric cancer stem cells and their effects on gastric cancer: Novel therapeutic targets for gastric cancer.Frontiers in oncology · 2022Review
- A promising antitumor method: Targeting CSC with immune cells modified with CAR.Frontiers in immunology · 2022Review
- Insight into the molecular mechanisms of gastric cancer stem cell in drug resistance of gastric cancer.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Resveratrol Analog 4-Bromo-Resveratrol Inhibits Gastric Cancer Stemness through the SIRT3-c-Jun N-Terminal Kinase Signaling Pathway.Current issues in molecular biology · 2021Article
- A tumour-resident Lgr5Nature cell biology · 2021Article
- Review
- LGR5 expression is associated with prognosis in poorly differentiated gastric adenocarcinoma.BMC cancer · 2021Article
- Early detection of tumor cells in bone marrow and peripheral blood in a fast‑progressing gastric cancer model.International journal of oncology · 2021Article
- ADNP prompts the cisplatin-resistance of bladder cancer via TGF-β-mediated epithelial-mesenchymal transition (EMT) pathway.Journal of Cancer · 2021Article
- The Regulatory Role of PRRX1 in Cancer Epithelial-Mesenchymal Transition.OncoTargets and therapy · 2021Review
- Lgr5 and stem/progenitor gene expression in gastric/gastroesophageal junction carcinoma - significance of potentially retained stemness.BMC cancer · 2020Article
- 2,4-Diamino-Quinazoline, a Wnt Signaling Inhibitor, Suppresses Gastric Cancer Progression and Metastasis.International journal of molecular sciences · 2020Article
- Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma.Cancers · 2020Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAccumulating evidence supports the hypothesis that cancer stem cells (CSCs) are essential for cancer initiation, metastasis and drug resistance. However, the functional association of gastric CSC markers with stemness and epithelial-mesenchymal transition (EMT) signature genes is unclear.
methodsqPCR was performed to measure the expression profiles of stemness and EMT signature genes and their association with putative CSC markers in gastric cancer tissues, cancer cell lines and sphere cells. Western blot analysis was used to confirm the results of the transcript analysis. Cell proliferation, cell migration, drug resistance and sphere cell growth assays were conducted to measure the expansion and invasion abilities of the cells. Tumor xenograft experiments were performed in NOD/SCID mice to test cell stemness in vivo. Flow cytometry and immunofluorescence staining were used to analyze cell subpopulations.
resultsThe expression of LGR5 was strikingly up-regulated in sphere cells but not in cancer tissues or parental adherent cells. The up-regulation of LGR5 was also positively associated with stemness regulators (NANOG, OCT4, SOX2, and AICDA) and EMT inducers (PRRX1, TWIST1, and BMI1). In addition, sphere cells exhibited up-regulated vimentin and down-regulated E-cadherin expression. Using gene-specific primers, we found that the NANOG expression primarily originates from the retrogene NANOGP8. Western blot analysis showed that the expression of both LGR5 and NANOG is significantly higher in sphere cells. LGR5 over-expression significantly enhanced sphere cell growth, cell proliferation, cell migration and drug resistance in MGC803 cells. Tumor xenografts in nude mice showed that sphere cells are at least 10 times more efficient at tumor initiation than adherent cells. Flow cytometry analysis showed that ~20% of sphere cells are LGR5+/CD54+, but only ~3% of adherent cells are Lgr5+/CD54+. Immunofluorescence staining supports the above results.
conclusionThe LGR5-expressing fraction of CD54+ cells represents gastric cancer CSCs, in which LGR5 is closely associated with stemness and EMT core genes, and NANOG expression is mainly contributed by the retrogene NANOGP8. Sphere cells are the best starting materials for the characterization of CSCs.
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