C-reactive protein binds to integrin α2 and Fcγ 3 receptor I, leading to breast cell adhesion and breast cancer progression

E. S. Kim, S. Y. Kim, M. Koh, H. M. Lee, K. Kim, J. Jung, H. S. Kim, W. K. Moon, Se-Jin Hwang, A. Moon

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 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 3 receptor Fcγ 3 receptor I (Fcγ 3RI), 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 Fcγ 3RI 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 Fcγ 3RI 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.

Original languageEnglish
Pages (from-to)28-38
Number of pages11
JournalOncogene
Volume37
Issue number1
DOIs
StatePublished - 2018 Jan 4

Fingerprint

Fc Receptors
Cell Adhesion
Integrins
C-Reactive Protein
Breast
Breast Neoplasms
Paxillin
Focal Adhesion Kinase 2
Triple Negative Breast Neoplasms
Focal Adhesion Protein-Tyrosine Kinases
Adhesives
Up-Regulation
Phenotype
Neoplasms
Acute-Phase Proteins
Growth
Matrix Metalloproteinases
Extracellular Matrix
Transcription Factors
Epithelial Cells

Cite this

Kim, E. S. ; Kim, S. Y. ; Koh, M. ; Lee, H. M. ; Kim, K. ; Jung, J. ; Kim, H. S. ; Moon, W. K. ; Hwang, Se-Jin ; Moon, A. / C-reactive protein binds to integrin α2 and Fcγ 3 receptor I, leading to breast cell adhesion and breast cancer progression. In: Oncogene. 2018 ; Vol. 37, No. 1. pp. 28-38.
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title = "C-reactive protein binds to integrin α2 and Fcγ 3 receptor I, leading to breast cell adhesion and breast cancer progression",
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 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 3 receptor Fcγ 3 receptor I (Fcγ 3RI), 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 Fcγ 3RI 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 Fcγ 3RI 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.",
author = "Kim, {E. S.} and Kim, {S. Y.} and M. Koh and Lee, {H. M.} and K. Kim and J. Jung and Kim, {H. S.} and Moon, {W. K.} and Se-Jin Hwang and A. Moon",
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C-reactive protein binds to integrin α2 and Fcγ 3 receptor I, leading to breast cell adhesion and breast cancer progression. / Kim, E. S.; Kim, S. Y.; Koh, M.; Lee, H. M.; Kim, K.; Jung, J.; Kim, H. S.; Moon, W. K.; Hwang, Se-Jin; Moon, A.

In: Oncogene, Vol. 37, No. 1, 04.01.2018, p. 28-38.

Research output: Contribution to journalArticle

TY - JOUR

T1 - C-reactive protein binds to integrin α2 and Fcγ 3 receptor I, leading to breast cell adhesion and breast cancer progression

AU - Kim, E. S.

AU - Kim, S. Y.

AU - Koh, M.

AU - Lee, H. M.

AU - Kim, K.

AU - Jung, J.

AU - Kim, H. S.

AU - Moon, W. K.

AU - Hwang, Se-Jin

AU - Moon, A.

PY - 2018/1/4

Y1 - 2018/1/4

N2 - 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 3 receptor Fcγ 3 receptor I (Fcγ 3RI), 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 Fcγ 3RI 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 Fcγ 3RI 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.

AB - 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 3 receptor Fcγ 3 receptor I (Fcγ 3RI), 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 Fcγ 3RI 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 Fcγ 3RI 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.

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