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C-reactive protein binds to integrin alpha 2 and Fc gamma receptor I, leading to breast cell adhesion and breast cancer progression

Title
C-reactive protein binds to integrin alpha 2 and Fc gamma receptor I, leading to breast cell adhesion and breast cancer progression
Author
황세진
Keywords
EPITHELIAL-CELLS; H-RAS; INVASIVE PHENOTYPE; ACUTE APPENDICITIS; TUMOR-GROWTH; EXPRESSION; PAXILLIN; KINASE; METASTASIS; INTERLEUKIN-6
Issue Date
2018-01
Publisher
NATURE PUBLISHING GROUP
Citation
ONCOGENE, v. 37, no. 1, page. 28-38
Abstract
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 alpha 2 signaling. Expression of integrin alpha 2 was induced by CRP in which transcription factors c-fos and SP1 may be involved. Binding of CRP with integrin alpha 2 leads to the activation of focal adhesion kinase (FAK), paxillin and ERKs. CRP also binds to an Fc gamma receptor Fc gamma receptor I (Fc gamma RI), and induces activation of paxillin, FAK and ERKs. Integrin alpha 2 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 Fc gamma RI and integrin alpha 2. Involvement of CRP in adhesion, invasion, anchorage-independent growth and upregulation of integrin alpha 2, 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 alpha 2 and Fc gamma RI 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.
URI
https://www.nature.com/articles/onc2017298http://repository.hanyang.ac.kr/handle/20.500.11754/117141
ISSN
0950-9232; 1476-5594
DOI
10.1038/onc.2017.298
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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