ArticleCancer research2007
E-cadherin cell-cell adhesion in ewing tumor cells mediates suppression of anoikis through activation of the ErbB4 tyrosine kinase.
Article in Cancer research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 184 citations in OpenAlex.
- ATG7-deficient fibroblast promotes breast cancer progression via exosome-mediated downregulation of SCARB1.Cell death & disease · 2025Article
- Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.Molecular oncology · 2025Article
- Effects of macrophages on the osteogenic differentiation of adipose tissue-derived stem cells in two-dimensional and three-dimensional cocultures.World journal of stem cells · 2025Article
- Measurement of adhesion and traction of cells at high yield reveals an energetic ratchet operating during nephron condensation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Comprehensive analysis of hub genes associated with cisplatin-resistance in ovarian cancer and screening of therapeutic drugs through bioinformatics and experimental validation.Journal of ovarian research · 2024Article
- Three-Dimensional Hepatocyte Spheroids: Model for Assessing Chemotherapy in Hepatocellular Carcinoma.Biomedicines · 2024Article
- Geometric tumor embolic budding characterizes inflammatory breast cancer.Breast cancer research and treatment · 2023Article
- Identification of anoikis-related molecular patterns to define tumor microenvironment and predict immunotherapy response and prognosis in soft-tissue sarcoma.Frontiers in pharmacology · 2023Article
- Plasma membrane proteoglycans syndecan-2 and syndecan-4 engage with EGFR and RON kinase to sustain carcinoma cell cycle progression.The Journal of biological chemistry · 2022Article
- Comparative characteristics of small cell lung cancer and Ewing's sarcoma: a narrative review.Translational lung cancer research · 2022Review
- Novel Targeted Therapeutic Strategies for Ewing Sarcoma.Cancers · 2022Review
- Semaphorin 3F induces colorectal cancer cell chemosensitivity by promoting P27 nuclear export.Frontiers in oncology · 2022Article
- E-Cadherin expression in human tumors: a tissue microarray study on 10,851 tumors.Biomarker research · 2021Article
- Morphofunctional analysis of human pancreatic cancer cell lines in 2- and 3-dimensional cultures.Scientific reports · 2021Article
- Article
- Monascin accelerates anoikis in circulating tumor cells and prevents breast cancer metastasis.Oncology letters · 2020Article
- Modeling the Tumor Microenvironment and Pathogenic Signaling in Bone Sarcoma.Tissue engineering. Part B, Reviews · 2020Review
- The Role of C-X-C Chemokine Receptor Type 4 (CXCR4) in Cell Adherence and Spheroid Formation of Human Ewing's Sarcoma Cells under Simulated Microgravity.International journal of molecular sciences · 2019Article
- Tissue-engineered 3D models for elucidating primary and metastatic bone cancer progression.Acta biomaterialia · 2019Review
- SOX18 Affects Cell Viability, Migration, Invasiveness, and Apoptosis in Hepatocellular Carcinoma (HCC) Cells by Participating in Epithelial-to-Mesenchymal Transition (EMT) Progression and Adenosine Monophosphate Activated Protein Kinase (AMPK)/Mammalian Target of Rapamycin (mTOR).Medical science monitor : international medical journal of experimental and clinical research · 2019Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Ability to grow under anchorage-independent conditions is one of the major hallmarks of transformed cells. Key to this is the capacity of cells to suppress anoikis, or programmed cell death induced by detachment from the extracellular matrix. To model this phenomenon in vitro, we plated Ewing tumor cells under anchorage-independent conditions by transferring them to dishes coated with agar to prevent attachment to underlying plastic. This resulted in marked up-regulation of E-cadherin and rapid formation of multicellular spheroids in suspension. Addition of calcium chelators, antibodies to E-cadherin (but not to other cadherins or beta(1)-integrin), or expression of dominant negative E-cadherin led to massive apoptosis of spheroid cultures whereas adherent cultures were unaffected. This correlated with reduced activation of the phosphatidylinositol 3-kinase-Akt pathway but not the Ras-extracellular signal-regulated kinase 1/2 cascade. Furthermore, spheroid cultures showed profound chemoresistance to multiple cytotoxic agents compared with adherent cultures, which could be reversed by alpha-E-cadherin antibodies or dominant negative E-cadherin. In a screen for potential downstream effectors of spheroid cell survival, we detected E-cadherin-dependent activation of the ErbB4 receptor tyrosine kinase but not of other ErbB family members. Reduction of ErbB4 levels by RNA interference blocked Akt activation and spheroid cell survival and restored chemosensitivity to Ewing sarcoma spheroids. Our results indicate that anchorage-independent Ewing sarcoma cells suppress anoikis through a pathway involving E-cadherin cell-cell adhesion, which leads to ErbB4 activation of the phosphatidylinositol 3-kinase-Akt pathway, and that this is associated with increased resistance of cells to cytotoxic agents.
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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.