CCN1/CYR61: the very model of a modern matricellular protein

Multi-author review

Abstract

CCN1 (CYR61) is a dynamically expressed, multifunctional matricellular protein that plays essential roles in cardiovascular development during embryogenesis, and regulates inflammation, wound healing and fibrogenesis in the adult. Aberrant CCN1 expression is associated with myriad pathologies, including various cancers and diseases associated with chronic inflammation. CCN1 promotes diverse and sometimes opposing cellular responses, which can be ascribed, as least in part, to disparate activities mediated through its direct binding to distinct integrins in different cell types and contexts. Accordingly, CCN1 promotes cell proliferation, survival and angiogenesis by binding to integrin αvβ3, and induces apoptosis and senescence through integrin α6β1 and heparan sulfate proteoglycans. The ability of CCN1 to trigger the accumulation of a robust and sustained level of reactive oxygen species underlies some of its unique activities as a matrix cell-adhesion molecule. Emerging studies suggest that CCN1 might be useful as a biomarker or therapeutic target in certain diseases.

Keywords

Angiogenesis Apoptosis Fibrosis Integrins Reactive oxygen species Senescence Signal transduction Tumorigenesis Wound healing 

Abbreviations

AVSD

Atrioventricular septal defects

CTGF

Connective tissue growth factor

CYR61

Cysteine-rich 61

ECM

Extracellular matrix

ERK

Extracellular signal-regulated kinase

GPCR

G protein-coupled receptor

HIF-1α

Hypoxia-inducible factor-1α

HIV-1

Human immunodeficiency virus type 1

HSPG

Heparan sulfate proteoglycan

IL

Interleukin

IRES

Internal ribosome entry sites

MMP

Matrix metalloproteinase

MRTF-A

Myocardin-related transcriptional activator

NSCLC

Non-small-cell lung cancer

NOV

Nephroblastoma overexpressed

ROS

Reactive oxygen species

SASP

Senescence-associated secretory phenotype

SRE

Serum response element

SRF

Serum response factor

TGF-β

Transforming growth factor β

TNF-α

Tumor necrosis factor α

TSR

Thrombospondin type I repeat

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© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular GeneticsUniversity of Illinois at Chicago College of MedicineChicagoUSA

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