ArticleOncotarget2017
The G-protein coupled receptor 56, expressed in colonic stem and cancer cells, binds progastrin to promote proliferation and carcinogenesis.
Article in Oncotarget, 2017. 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, 51 citations in OpenAlex.
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Progastrin, annexin A2, and tumor-associated macrophages in gastric adenocarcinoma.Journal of pathology and translational medicine · 2026Article
- GPCR Biased Signaling in Cancer.Handbook of experimental pharmacology · 2026Review
- Progastrin Promotes Colorectal Cancer Stem Cell-Like Properties via the Receptor PZR.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanosensitive adhesion G protein-coupled receptors: Insights from health and disease.Genes & diseases · 2025Review
- G protein selectivity profile of GPR56/ADGRG1 and its effect on downstream effectors.Research square · 2024Article
- G protein selectivity profile of GPR56/ADGRG1 and its effect on downstream effectors.Cellular and molecular life sciences : CMLS · 2024Article
- Relationship betweenWorld journal of gastrointestinal surgery · 2024Article
- Progastrin: An Overview of Its Crucial Role in the Tumorigenesis of Gastrointestinal Cancers.Biomedicines · 2024Review
- Hexahydroquinoline Derivatives Are Selective Agonists for the Adhesion G Protein-Coupled Receptor ADGRG1/GPR56.Molecular pharmacology · 2023Article
- Effects of hormones on intestinal stem cells.Stem cell research & therapy · 2023Review
- An antibody-drug conjugate targeting GPR56 demonstrates efficacy in preclinical models of colorectal cancer.British journal of cancer · 2023Article
- Role of Adhesion G Protein-Coupled Receptors in Immune Dysfunction and Disorder.International journal of molecular sciences · 2023Review
- Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology.Physiological reviews · 2022Review
- Ligands and Beyond: Mechanosensitive Adhesion GPCRs.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Multi-Omics Analysis of Glioblastoma and Glioblastoma Cell Line: Molecular Insights Into the Functional Role of GPR56 and TG2 in Mesenchymal Transition.Frontiers in oncology · 2022Article
- Article
- Progress in elucidating the relationship betweenWorld journal of gastroenterology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Overexpression of human progastrin increases colonic mucosal proliferation and colorectal cancer progression in mice. The G-protein coupled receptor 56 (GPR56) is known to regulate cell adhesion, migration, proliferation and stem cell biology, but its expression in the gut has not been studied. We hypothesized that the promotion of colorectal cancer by progastrin may be mediated in part through GPR56. Here, we found that GPR56 expresses in rare colonic crypt cells that lineage trace colonic glands consistent with GPR56 marking long-lived colonic stem-progenitor cells. GPR56 was upregulated in transgenic mice overexpressing human progastrin. While recombinant human progastrin promoted the growth and survival of wild-type colonic organoids in vitro, colonic organoids cultured from GPR56-/- mice were resistant to progastrin. We found that progastrin directly bound to, and increased the proliferation of, GPR56-expressing colon cancer cells in vitro, and proliferation was increased in cells that expressed both GPR56 and the cholecystokinin-2 receptor (CCK2R). In vivo, deletion of GPR56 in the mouse germline abrogated progastrin-dependent colonic mucosal proliferation and increased apoptosis. Loss of GPR56 also inhibited progastrin-dependent colonic crypt fission and colorectal carcinogenesis in the azoxymethane (AOM) mouse model of colorectal cancer. Overall, we found that progastrin binds to GPR56 expressing colonic stem cells, which in turn promotes their expansion, and that this GPR56-dependent pathway is an important driver and potential new target in colorectal carcinogenesis.
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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.