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

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.

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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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Acknowledgments

I thank Chih-Chiun Chen and Joon-Il Jun for helpful comments on the manuscript. This work was supported by grants (CA46565, GM78492 and HL81390) from the National Institutes of Health.

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Correspondence to Lester F. Lau.

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Lau, L.F. CCN1/CYR61: the very model of a modern matricellular protein. Cell. Mol. Life Sci. 68, 3149 (2011). https://doi.org/10.1007/s00018-011-0778-3

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Keywords

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