ArticleJournal of experimental & clinical cancer research : CR2023
Exosomal circTUBGCP4 promotes vascular endothelial cell tipping and colorectal cancer metastasis by activating Akt signaling pathway.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 65 citations in OpenAlex.
- Exosomal PKM2 from AML cells reprograms endothelial metabolism to promote angiogenesis and chemoresistance.Functional & integrative genomics · 2026Article
- Circular RNAs in cancer: Its biogenesis, functions, relationships with cancer progression, applications in immunotherapy and biomarker potentials.Cancer immunology, immunotherapy : CII · 2026Review
- RNA Regulatory Networks: Key Hubs in the Panorama of Cancer and Emerging Therapeutic Targets.MedComm · 2026Review
- Review
- Exosome Augmentation Technologies for Drug Delivery and Disease Treatment: A Review.Biomaterials research · 2026Review
- The role of extracellular vesicles in the transport and regulation of novel inflammatory mediators in IBD and its associated CRC.Frontiers in cell and developmental biology · 2026Review
- Extracellular vesicles cargo orchestration in colorectal cancer: immune evasion, stromal remodeling, and therapeutic frontiers.Molecular cancer · 2025Review
- Regulatory roles of non-coding and exosomal RNAs in colorectal cancer: spotlight on angiogenesis.Clinical and experimental medicine · 2025Review
- Circular RNAs and endothelial dysfunction: mechanistic crosstalk and emerging therapeutic perspectives.Cellular and molecular life sciences : CMLS · 2025Review
- Fibronectin 1 Aggravates Colon Cancer Metastasis by Regulating RAP1B Protein Stability Through Akt/CREB Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Predicting lung metastasis in high-grade Osteosarcoma: The role of CTA Signs, with a Focus on vascular wrapping and intratumoral vascular network.Journal of bone oncology · 2025Article
- Competitive binding between DDX21 and SIRT7 enhances NAT10-mediated acCell death & disease · 2025Article
- Advances in the roles and molecular mechanisms of exosomal circular RNAs in regulating the pre-metastatic niche of tumors.Discover oncology · 2025Review
- CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25-Mediated Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Blockade of Exosome Release Sensitizes Breast Cancer to Doxorubicin via Inhibiting Angiogenesis.Cancer medicine · 2025Article
- Invasion and metastasis in cancer: molecular insights and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition.Journal of biomedical science · 2025Article
- Exosomal Non-Coding RNAs in Pancreatic Cancer: From Mechanisms to Clinical Applications.Oncology research · 2025Review
- Exosomal CircRNAs: A Future Star in Colorectal Cancer.Current cancer drug targets · 2025Review
- Exosomal miR-320d promotes angiogenesis and colorectal cancer metastasis via targeting GNAI1 to affect the JAK2/STAT3 signaling pathway.Cell death & disease · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundExosome is crucial mediator and play an important role in tumor angiogenesis. Tip cell formation is a prerequisite for persistent tumor angiogenesis which causes tumor metastasis. However, the functions and underlying mechanisms of tumor cell-derived exosomes in angiogenesis and tip cell formation remain less understood.
methodsExosomes derived from serum of colorectal cancer (CRC) patients with metastasis/non-metastasis and CRC cells were isolated by ultracentrifugation. CircRNAs in these exosomes were analyzed by circRNA microarray. Then, exosomal circTUBGCP4 was identified and verified by quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Loss- and gain-of-function assays were performed to explore the effect of exosomal circTUBGCP4 on vascular endothelial cell tipping and colorectal cancer metastasis in vitro and in vivo. Mechanically, bioinformatics analysis, biotin-labeled circTUBGCP4/ miR-146b-3p RNA pulldown, RNA immunoprecipitation (RIP), and luciferase reporter assay were used to confirm the interaction among circTUBGCP4, miR-146b-3p, and PDK2.
resultsHere, we showed that exosomes derived from CRC cells enhanced vascular endothelial cell migration and tube formation via inducing filopodia formation and endothelial cell tipping. We further screened the upregulated circTUBGCP4 in serum of CRC patients with metastasis compared to non-metastasis. Silencing circTUBGCP4 expression in CRC cell-derived exosomes (CRC-CDEs) inhibited endothelial cell migration, tube formation, tip cell formation, and CRC metastasis. Overexpression of circTUBGCP4 had opposite results in vitro and in vivo. Mechanically, circTUBGCP4 upregulated PDK2 to activate Akt signaling pathway by sponging miR-146b-3p. Moreover, we found that miR-146b-3p could be a key regulator for vascular endothelial cell dysfunction. Exosomal circTUBGCP4 promoted tip cell formation and activated the Akt signaling pathway by inhibiting miR-146b-3p.
conclusionsOur results suggest that colorectal cancer cells generate exosomal circTUBGCP4, which causes vascular endothelial cell tipping to promote angiogenesis and tumor metastasis by activating Akt signaling pathway.
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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.