ArticleCell research2016
Gastric Lgr5(+) stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice.
Article in Cell research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 99 citations in OpenAlex.
- Review
- Review
- Regulation and Function of Sox2 and CD44 Expression in the Stomach by Bone Morphogenetic Protein Signaling.Gastro hep advances · 2026Article
- Precancerous pathways to gastric cancer: a review of experimental animal models recapitulating the correa cascade.Frontiers in cell and developmental biology · 2025Review
- Identification of gastric cancer stem cells with CD44 and Lgr5 double labelling and their initial roles on gastric cancer malignancy and chemotherapy resistance.Cell biology and toxicology · 2024Article
- Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.eLife · 2024Article
- Article
- CCKBR+ cancer cells contribute to the intratumor heterogeneity of gastric cancer and confer sensitivity to FOXO inhibition.Cell death and differentiation · 2024Article
- Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.bioRxiv : the preprint server for biology · 2024Article
- Review
- POLQ inhibition attenuates the stemness and ferroptosis resistance in gastric cancer cells via downregulation of dihydroorotate dehydrogenase.Cell death & disease · 2024Article
- Gastric intestinal metaplasia: progress and remaining challenges.Journal of gastroenterology · 2024Review
- Helicobacter pylori-activated fibroblasts as a silent partner in gastric cancer development.Cancer metastasis reviews · 2023Review
- Expression of Stem Cell Markers in High-LET Space Radiation-Induced Intestinal Tumors inCancers · 2023Article
- Cancer stem cells: an insight into the development of metastatic tumors and therapy resistance.Stem cell reviews and reports · 2023Review
- The composition and roles of gastric stem cells in epithelial homeostasis, regeneration, and tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study.BMC cancer · 2023Article
- Roles of cancer stem cells in gastrointestinal cancers.World journal of stem cells · 2023Review
- Gastric precancerous lesions:occurrence, development factors, and treatment.Frontiers in oncology · 2023Review
- Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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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
The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5(+) stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5(+) stem cells by the inducible Cre-LoxP system and marked mutant Lgr5(+) stem cells and their progeny with Cre-reporter Rosa26(tdTomato). Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5(+) stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5(+) chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5(+) cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5(+) stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression.
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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.