C‐reactive Protein Binds to Integrin α2 and Fcγ receptor I, Leading to Breast Cell Adhesion and Breast Cancer Progression
| العنوان: | C‐reactive Protein Binds to Integrin α2 and Fcγ receptor I, Leading to Breast Cell Adhesion and Breast Cancer Progression |
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| المؤلفون: | Aree Moon, Kyoung Mee Kim, Hyunsook Lee, Sejin Hwang, Joohee Jung, H. S. Kim, S. Y. Kim, W. K. Moon, M. Koh, Eun Sook Kim |
| المصدر: | The FASEB Journal. 32 |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Integrin alpha2, Biochemistry, Mice, 0302 clinical medicine, Cell Movement, Breast, RNA, Small Interfering, skin and connective tissue diseases, Receptor, Mice, Inbred BALB C, biology, Chemistry, Cell biology, Up-Regulation, Gene Expression Regulation, Neoplastic, C-Reactive Protein, Integrin alpha M, 030220 oncology & carcinogenesis, Gene Knockdown Techniques, Disease Progression, Integrin, beta 6, Female, Signal Transduction, Biotechnology, Integrin, Mice, Nude, Breast Neoplasms, Focal adhesion, 03 medical and health sciences, Breast cancer, Cell Line, Tumor, Cell Adhesion, Genetics, medicine, Animals, Humans, Autocrine signalling, Cell adhesion, Molecular Biology, Paxillin, Receptors, IgG, C-reactive protein, Intravasation, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Cancer research, biology.protein |
| الوصف: | C-reactive protein (CRP) is an acute phase protein synthesized upon the inflammatory responses, associated with breast cancer. The process of tumor cell invasion and metastasis involves the adherence of cells to the extracellular matrix via integrin as a receptor for matrix molecules. The present study investigated the role of CRP in the adhesive phenotype of breast cells and the underlying mechanisms. Here, we first showed that CRP induces adhesion of MCF10A human breast epithelial cells through the activation of integrin α2 signaling. Expression of integrin α2 was induced by CRP in which transcription factors c-fos and SP1 may be involved. Binding of CRP with integrin α2 leads to the activation of focal adhesion kinase (FAK), paxillin and ERKs. CRP also binds to an Fcγ receptor Fcγ receptor I (FcγRI), and induces activation of paxillin, FAK and ERKs. Integrin α2 and FAK have crucial roles in the adhesive and invasive phenotypes as well as MMP-9 upregulation induced by CRP in MCF10A cells. Treatment with an inflammatory lipid sphingosine-1-phosphate induced CRP, which may be secreted and exert an autocrine effect by binding to FcγRI and integrin α2. Involvement of CRP in adhesion, invasion, anchorage-independent growth and upregulation of integrin α2, paxillin and FAK was observed in MDA-MB-231 triple-negative human breast cancer (TNBC) cells. Using an in vivo invasion model and an orthotopic mouse tumor model with MDA-MB-231 cells, we showed that CRP has an important role in intravasation and tumor growth in vivo, demonstrating the in vivo relevance of our in vitro results. The present study elucidates a critical molecular basis between CRP, integrin α2 and FcγRI pathways in MCF10A breast cells and MDA-MB-231 TNBC cells, thereby providing useful information on CRP-induced aggressiveness of breast cells in the inflammatory microenvironment. |
| تدمد: | 1530-6860 0892-6638 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::69a414b8199fd7848bba99395af4d667Test https://doi.org/10.1096/fasebj.2018.32.1_supplement.533.1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....69a414b8199fd7848bba99395af4d667 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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