ArticleNeoplasia (New York, N.Y.)2012
Membrane-bound and exosomal metastasis-associated C4.4A promotes migration by associating with the α(6)β(4) integrin and MT1-MMP.
Article in Neoplasia (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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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.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Pathways and outputs orchestrated in tumor microenvironment cells by hypoxia-induced tumor-derived exosomes in pan-cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Review
- Circadian regulation of protein cargo in extracellular vesicles.Science advances · 2022Article
- Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects.Frontiers in immunology · 2022Review
- Distinct Cargos of Small Extracellular Vesicles Derived from Hypoxic Cells and Their Effect on Cancer Cells.International journal of molecular sciences · 2020Review
- β2-Adrenergic Signalling Promotes Cell Migration by Upregulating Expression of the Metastasis-Associated Molecule LYPD3.Biology · 2020Article
- Crystal Structures of Human C4.4A Reveal the Unique Association of Ly6/uPAR/α-neurotoxin Domain.International journal of biological sciences · 2020Article
- Decreasing Microtubule Actin Cross-Linking Factor 1 Inhibits Melanoma Metastasis by Decreasing Epithelial to Mesenchymal Transition.Cancer management and research · 2020Article
- The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer.Cell reports · 2019Article
- Exosome-orchestrated hypoxic tumor microenvironment.Molecular cancer · 2019Review
- Review
- The key role of extracellular vesicles in the metastatic process.Biochimica et biophysica acta. Reviews on cancer · 2018Review
- De novo synthesis of C4.4A in hepatocellular carcinoma promotes migration and invasion of tumor cells.Oncology reports · 2017Article
- Association of Extracellular Membrane Vesicles with Cutaneous Wound Healing.International journal of molecular sciences · 2017Review
- Going live with tumor exosomes and microvesicles.Cell adhesion & migration · 2017Review
- Developments in miRNA gene signaling pathways in pancreatic cancer.Future oncology (London, England) · 2016Review
- Organization, evolution and functions of the human and mouse Ly6/uPAR family genes.Human genomics · 2016Review
- A small molecule induces integrin β4 nuclear translocation and apoptosis selectively in cancer cells with high expression of integrin β4.Oncotarget · 2016Article
- Decreasing lncRNA HOTAIR expression inhibits human colorectal cancer stem cells.American journal of translational research · 2016Article
- New Blocking Antibodies against Novel AGR2-C4.4A Pathway Reduce Growth and Metastasis of Pancreatic Tumors and Increase Survival in Mice.Molecular cancer therapeutics · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis-associated C4.4A, which becomes upregulated during wound healing and, in some tumors, during tumor progression, is known to be frequently associated with hypoxia. With the function of C4.4A still unknown, we explored the impact of hypoxia on C4.4A expression and functional activity. Metastatic rat and human tumor lines upregulate C4.4A expression when cultured in the presence of CoCl(2). Although hypoxia-inducible factor 1α (HIF-1α) becomes upregulated concomitantly, HIF-1α did not induce C4.4A transcription. Instead, hypoxia-induced C4.4A up-regulation promoted in vivo and in vitro wound healing, where increased migration on the C4.4A ligands laminin-111 and -332 was observed after a transient period of pronounced binding. Increased migration was accompanied by C4.4A associating with α(6)β(4), MT1-MMP1, and TACE and by laminin fragmentation. Hypoxia also promoted the release of C4.4A in exosomes and TACE-mediated C4.4A shedding. The association of C4.4A with α(6)β(4) and MT1-MMP1 was maintained in exosomes and exosomal α(6)β(4)- and MT1-MMP1-associated C4.4A but not shed C4.4A sufficient for laminin degradation. Hypoxia-induced recruitment of α(6)β(4) toward raft-located C4.4A, MT1-MMP, and TACE allows for a shift from adhesion to motility, which is supported by laminin degradation. These findings provide the first explanation for the C4.4A contribution to wound healing and metastasis.
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