ArticleGut2016
Gastric tumour-derived ANGPT2 regulation by DARPP-32 promotes angiogenesis.
Article in Gut, 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, 57 citations in OpenAlex.
- Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial.British journal of cancer · 2016Trial
- Article
- NNMT/1-MNA protects against hepatic ischemia-reperfusion injury through the AKT/FOXO1/ANGPT2/JNK axis.Nature communications · 2025Article
- Therapeutic Targets for Gastric Cancer: Mendelian Randomization and Colocalization Analysis.Biological procedures online · 2025Article
- Integrated proteogenomic characterization of ampullary adenocarcinoma.Cell discovery · 2025Article
- Immunohistochemical characterization and potential prognostic relevance of dopamine signaling in canine pulmonary adenocarcinoma.Frontiers in veterinary science · 2025Article
- The Role of Dopamine in Gastric Cancer-A Systematic Review of the Pathogenesis Phenomena Developments.Biomedicines · 2024Review
- Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer.Cell reports. Medicine · 2024Article
- RBM15 Protects From Myocardial Infarction by Stabilizing NAE1.JACC. Basic to translational science · 2024Article
- Evaluation of t-DARPP Expression Alteration in Association with DDR1 Expression in Non-Small Cell Lung Cancer.Iranian biomedical journal · 2024Article
- Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 promotes colorectal cancer growth.World journal of gastrointestinal oncology · 2023Article
- IKKα promotes lung adenocarcinoma growth through ERK signaling activation via DARPP-32-mediated inhibition of PP1 activity.NPJ precision oncology · 2023Article
- MYBL1 induces transcriptional activation of ANGPT2 to promote tumor angiogenesis and confer sorafenib resistance in human hepatocellular carcinoma.Cell death & disease · 2022Article
- Circulating proteins and risk of pancreatic cancer: a case-subcohort study among Chinese adults.International journal of epidemiology · 2022Article
- DARPP-32 promotes ERBB3-mediated resistance to molecular targeted therapy in EGFR-mutated lung adenocarcinoma.Oncogene · 2022Article
- Ang2-Targeted Combination Therapy for Cancer Treatment.Frontiers in immunology · 2022Review
- miR‑135a‑5p inhibits tumor invasion by targeting ANGPT2 in gallbladder cancer.Molecular medicine reports · 2021Article
- Exploiting a New Approach to Destroy the Barrier of Tumor Microenvironment: Nano-Architecture Delivery Systems.Molecules (Basel, Switzerland) · 2021Review
- Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer.BMC gastroenterology · 2021Article
- Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveOverexpression of dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32), and its truncated isoform (t-DARPP) are associated with gastric tumorigenesis. Herein, we investigated the role of DARPP-32 proteins in regulating angiopoietin 2 (ANGPT2) and promoting tumour angiogenesis.
designQuantitative real-time RT-PCR, immunoblotting, luciferase reporter, immunofluorescence, immunohistochemistry and angiogenesis assays were applied to investigate the regulation of angiogenesis by DARPP-32 proteins.
resultsOverexpression of DARPP-32 significantly increased the mRNA and protein levels of ANGPT2 in gastric cancer cells. The overexpression of DARPP-32 T34A mutant or the N-terminal truncated isoform, t-DARPP, led to similar effects ruling out the T34-dependent regulation of protein phosphatase 1 activity in regulating ANGPT2. DARPP-32 proteins induced a secreted form of ANGPT2, which was detectable in the media, functionally active, and able to induce angiogenesis, measured by the human umbilical vein endothelial cells tube formation assay. Antibody blocking of the secreted ANGPT2 abrogated its function. To identify the mechanism by which DARPP-32 regulates ANGPT2, we examined the activities of NF-κB and signal transducer and activator of transcription 3 (STAT3), known regulators of angiogenesis. The results ruled out NF-κB and showed induction of STAT3 phosphorylation, activation and nuclear localisation. Inhibition or knockdown of STAT3 significantly attenuated the induction of ANGPT2 by DARPP-32 proteins. In vivo xenograft models demonstrated that overexpression of DARPP-32 promotes angiogenesis and tumour growth. Analyses of human gastric cancer tissues showed a strong correlation between DARPP-32 and ANGPT2.
conclusionsOur novel findings establish the role of DARPP-32-STAT3 axis in regulating ANGPT2 in cancer cells to promote angiogenesis and tumorigenesis.
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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.