ArticleJournal of experimental & clinical cancer research : CR2020
Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
- The immune phenotype of circulating tumor cells: from escape mechanisms to immunotherapy navigation.Biomarker research · 2026Review
- Review
- Role of ATOH8 in Mitigating Cardiac Fibrosis in Heart Failure via Inhibition of the Transcriptional Repression of Smad7 by RUNX2.Biomolecules & therapeutics · 2026Article
- Mechanoadaptation via Myosin Cytoplasmic Redistribution Protects Circulating Tumor Cells From Shear-induced Death During Hematogenous Dissemination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Brief pulses of high-level fluid shear stress enhance metastatic potential and rapidly alter the metabolism of cancer cells.Cell reports · 2026Article
- ROS-sensitive liposomal co-delivery of photosensitizer, factor Xa inhibitor, and PD-L1 blockade enhances photodynamic immunotherapy.Theranostics · 2026Article
- Circulating Tumor Cells for the Monitoring of Lung Cancer Therapies.International journal of molecular sciences · 2025Review
- Clinical significance of preoperative serum VEGF in predicting metachronous liver metastasis of colorectal cancer: development of a novel nomogram.World journal of surgical oncology · 2025Article
- Cinobufagin inhibits hepatocellular carcinoma EMT-like stemness via VEGF/VEGFR2 autocrine signaling.Discover oncology · 2025Article
- Exploring Novel Therapeutic Targets in Breast Cancer via Comprehensive Omics Profiling and Experimental Verification.Biology · 2025Article
- "Friends or foes": a new perspective of tumour metabolic transcriptional modification.Cell death & disease · 2025Review
- FXR1 associates with and degrades PDZK1IP1 and ATOH8 mRNAs and promotes esophageal cancer progression.Biology direct · 2024Article
- Mechanisms of microRNA Regulation of the Epithelial-Mesenchymal Transition (EMT) in Lung Cancer.Life (Basel, Switzerland) · 2024Review
- Effects of simulated microgravity on colorectal cancer organoids growth and drug response.Scientific reports · 2024Article
- Circulating tumor cells: from new biological insights to clinical practice.Signal transduction and targeted therapy · 2024Review
- Increase in Vascular Endothelial Growth Factor (VEGF) Expression and the Pathogenesis of iMCD-TAFRO.Biomedicines · 2024Review
- Review
- Advances in cancer mechanobiology: Metastasis, mechanics, and materials.APL bioengineering · 2024Review
- ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis.Gland surgery · 2024Article
- Phenotypic Heterogeneity, Bidirectionality, Universal Cues, Plasticity, Mechanics, and the Tumor Microenvironment Drive Cancer Metastasis.Biomolecules · 2024Review
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundMetastasis and recurrence, wherein circulating tumour cells (CTCs) play an important role, are the leading causes of death in colorectal cancer (CRC). Metastasis-initiating CTCs manage to maintain intravascular survival under anoikis, immune attack, and importantly shear stress; however, the underlying mechanisms remain poorly understood.
methodsIn view of the scarcity of CTCs in the bloodstream, suspended colorectal cancer cells were flowed into the cyclic laminar shear stress (LSS) according to previous studies. Then, we detected these suspended cells with a CK8+/CD45-/DAPI+ phenotype and named them mimic circulating tumour cells (m-CTCs) for subsequent CTCs related researches. Quantitative polymerase chain reaction, western blotting, and immunofluorescence were utilised to analyse gene expression change of m-CTCs sensitive to LSS stimulation. Additionally, we examined atonal bHLH transcription factor 8 (ATOH8) expressions in CTCs among 156 CRC patients and mice by fluorescence in situ hybridisation and flow cytometry. The pro-metabolic and pro-survival functions of ATOH8 were determined by glycolysis assay, live/dead cell vitality assay, anoikis assay, and immunohistochemistry. Further, the concrete up-and-down mechanisms of m-CTC survival promotion by ATOH8 were explored.
resultsThe m-CTCs actively responded to LSS by triggering the expression of ATOH8, a fluid mechanosensor, with executive roles in intravascular survival and metabolism plasticity. Specifically, ATOH8 was upregulated via activation of VEGFR2/AKT signalling pathway mediated by LSS induced VEGF release. ATOH8 then transcriptionally activated HK2-mediated glycolysis, thus promoting the intravascular survival of colorectal cancer cells in the circulation.
conclusionsThis study elucidates a novel mechanism that an LSS triggered VEGF-VEGFR2-AKT-ATOH8 signal axis mediates m-CTCs survival, thus providing a potential target for the prevention and treatment of hematogenous metastasis in CRC.
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