황세진
2019-12-04T04:37:32Z
2019-12-04T04:37:32Z
2018-01
ONCOGENE, v. 37, no. 1, page. 28-38
0950-9232
1476-5594
https://www.nature.com/articles/onc2017298
https://repository.hanyang.ac.kr/handle/20.500.11754/117141
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.
The present study was supported by Priority Research Centers Program (no. 2016R1A6A1A03007648), the Bio & Medical Technology Development Program (no. 2015M3A9B6074045) and Basic Science Program (no. 2014R1A6A3A01059908) of the NRF funded by the Korean government.
en_US
NATURE PUBLISHING GROUP
EPITHELIAL-CELLS
H-RAS
INVASIVE PHENOTYPE
ACUTE APPENDICITIS
TUMOR-GROWTH
EXPRESSION
PAXILLIN
KINASE
METASTASIS
INTERLEUKIN-6
C-reactive protein binds to integrin alpha 2 and Fc gamma receptor I, leading to breast cell adhesion and breast cancer progression
Article
1
37
10.1038/onc.2017.298
28-38
ONCOGENE
Kim, E-S
Kim, S. Y.
Koh, M.
Lee, H-M
Kim, K.
Jung, J.
Kim, H. S.
Moon, W. K.
Hwang, S.
Moon, A.
2018000045
S
COLLEGE OF MEDICINE[S]
DEPARTMENT OF MEDICINE
hwangsj