ArticleMolecular carcinogenesis2014
Reg4-induced mitogenesis involves Akt-GSK3β-β-Catenin-TCF-4 signaling in human colorectal cancer.
Article in Molecular carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly.World journal of gastroenterology · 2023Pooled it
- Overexpression of regenerating islet-derived type 4 isoform 2 increases colorectal cancer cell proliferation.Biochemistry and biophysics reports · 2026Article
- The VAX2-SERPINE1 axis modulates colorectal cancer cell proliferation and apoptosis through WNT/beta-catenin signaling.Translational oncology · 2026Article
- REG/Reg family proteins: mediating gut microbiota homeostasis and implications in digestive diseases.Gut microbes · 2025Review
- The Reg gene family: roles in gastric and colorectal cancer progression and its potential for targeted therapy.Discover oncology · 2025Review
- Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration.International journal of molecular sciences · 2022Article
- Upregulation of REG IV gene in human intestinal epithelial cells by lipopolysaccharide via downregulation of microRNA-24.Journal of cellular and molecular medicine · 2022Article
- REG4 promotes the proliferation and anti-apoptosis of cancer.Frontiers in cell and developmental biology · 2022Review
- The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract.International journal of molecular sciences · 2021Review
- Heat Shock Protein 90 Triggers Multi-Drug Resistance of Ovarian Cancer via AKT/GSK3β/β-Catenin Signaling.Frontiers in oncology · 2021Article
- Solasodine, Isolated fromDrug design, development and therapy · 2021Article
- Ibuprofen disrupts a WNK1/GSK3β/SRPK1 protein complex required for expression of tumor-related splicing variant RAC1B in colorectal cells.Oncotarget · 2020Article
- The Clinical Significance and Mechanisms of REG4 in Human Cancers.Frontiers in oncology · 2020Review
- REG4 is an indicator for KRAS mutant lung adenocarcinoma with TTF-1 low expression.Journal of cancer research and clinical oncology · 2019Article
- Four Decades After the Discovery of Regenerating Islet-Derived (Reg) Proteins: Current Understanding and Challenges.Frontiers in cell and developmental biology · 2019Review
- Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β-catenin signaling pathway in breast cancer.Cancer medicine · 2018Article
- Prognostic value of circulating vitamin D binding protein, total, free and bioavailable 25-hydroxy vitamin D in patients with colorectal cancer.Oncotarget · 2017Article
- Compound Wumei Powder Inhibits the Invasion and Metastasis of Gastric Cancer via Cox-2/PGE2-PI3K/AKT/GSK3Evidence-based complementary and alternative medicine : eCAM · 2017Article
- Recombinant Reg3β protein protects against streptozotocin-induced β-cell damage and diabetes.Scientific reports · 2016Article
- REG4 promotes peritoneal metastasis of gastric cancer through GPR37.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Upregulation of regenerating gene 4 (Reg4) is observed in many human gastrointestinal malignancies including colorectal cancer (CRC). We previously reported a Reg4-mediated induction of epidermal growth factor receptor-Akt-AP1 signaling regulating CRC cell apoptosis. However, the role of Reg4 in the regulation of CRC cell division is poorly understood. This study tests the hypothesis that Reg4 induces Akt-GSK3β-β-Catenin-TCF-4 signaling to regulate CRC cell division. In vitro models of human CRC were used to determine the role of Reg4 in regulation of CRC cell division. Cell cycle studies demonstrated that Reg4 treatment significantly decreased CRC cell number in G1 phase and increased in G2 phase. Subsequently Reg4 significantly increased the mitotic index of CRC cells. As assessed by real-time RT-PCR and Western blot analyses, Reg4 significantly increased the expression of cell cycle regulatory genes Cyclin D1 and D3, and associated Cyclin-dependent kinases (CDK4 and CDK6). Reg4-mediated increase in these genes involved a pathway that included an induced Akt activity by increasing phosphorylation of Thr308 and Ser473, a reduced glycogen synthase kinase 3β (GSK-3β) activity by increasing phosphorylation of Ser9, an induced nuclear translocation of β-Catenin by decreasing phosphorylation of Ser33/37/Thr41, and an increased TCF-4 transcriptional activity. Furthermore, antagonism of Reg4-signaling using Reg4-specific mAbs (2H6 and 3E5) and Akt inhibitor significantly decreased, whereas agonism using GSK-3β antagonist (SB216763) significantly increased mitotic index and proliferation of CRC cells. These results identify Reg4 as a key regulator of the CRC cell division and proliferation, hence a potential target of human CRC treatment.
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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.