Functions and mechanisms of action of CCN matricellular proteins

Chen, Chih-Chiun; Lau, Lester F.

doi:10.1016/j.biocel.2008.07.025

Cited by 549Connective Tissue Growth Factor ResearchBone and Dental Protein StudiesSignaling Pathways in Disease

Functions and mechanisms of action of CCN matricellular proteins

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Chen, Chih-Chiun, Lau, Lester F.·2009·The International Journal of Biochemistry & Cell Biology

DOI 10.1016/j.biocel.2008.07.025PMC PMC2668982

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Abstract

Members of the CCN (CYR61/CTGF/NOV) family have emerged as dynamically expressed, extracellular matrix-associated proteins that play critical roles in cardiovascular and skeletal development, injury repair, fibrotic diseases and cancer. The synthesis of CCN proteins is highly inducible by serum growth factors, cytokines, and environmental stresses such as hypoxia, UV exposure, and mechanical stretch. Consisting of six secreted proteins in vertebrate species, CCNs are typically comprised of four conserved cysteine-rich modular domains. They function primarily through direct binding to specific integrin receptors and heparan sulfate proteoglycans, thereby triggering signal transduction events that culminate in the regulation of cell adhesion, migration, proliferation, gene expression, differentiation, and survival. CCN proteins can also modulate the activities of several growth factors and cytokines, including TGF-beta, TNFalpha, VEGF, BMPs, and Wnt proteins, and may thereby regulate a broad array of biological processes. Recent studies have uncovered novel CCN activities unexpected for matricellular proteins, including their ability to induce apoptosis as cell adhesion substrates, to dictate the cytotoxicity of inflammatory cytokines such as TNFalpha, and to promote hematopoietic stem cell self-renewal. As potent regulators of angiogenesis and chondrogenesis, CCNs are essential for successful cardiovascular and skeletal development during embryogenesis. In the adult, the expression of CCN proteins is associated with injury repair and inflammation, and has been proposed as diagnostic or prognostic markers for diabetic nephropathy, hepatic fibrosis, systemic sclerosis, and several types of cancer. Targeting CCN signaling pathways may hold promise as a strategy of rational therapeutic design.

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CCN1 supports cell adhesion and induces adhesive signaling in many adherent cell types.
“This observation led to the finding that CCN1 can support cell adhesion and induce adhesive signaling in many adherent cell types [18,53].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [18]

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Authors: Chen, C.-C., & Lau, L. F.
Affiliations: University of Illinois Chicago (US)
Corresponding author: Lau, Lester F.
ORCID: Lau, Lester F.
Venue: The International Journal of Biochemistry & Cell Biology
Publisher: Elsevier BV
Published: 2009-04
Volume: 41
Issue: 4
Pages: 771-783
ISSN: 1357-2725 (ISSN-L)
DOI: 10.1016/j.biocel.2008.07.025
PMC: PMC2668982
OpenAlex: W2053865773
Cited by: 549
References: 161
Citations by year: 2026: 11 · 2025: 18 · 2024: 16 · 2023: 13 · 2022: 17 · 2021: 29 · 2020: 20 · 2019: 20 · 2018: 24 · 2017: 22 · 2016: 42 · 2015: 46 · 2014: 54 · 2013: 51 · 2012: 47
FWCI: 3.01
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: The International Journal of Biochemistry & Cell Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL081390, HL81390)
National Cancer Institute (R01CA046565, CA-46565)
National Institute of General Medical Sciences (R01GM078492, GM78492)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: CCN proteins, CYR61, connective tissue growth factor, NOV, matricellular proteins, extracellular matrix, integrin binding, heparan sulfate proteoglycans, signal transduction, cell adhesion, cell migration, TGF-beta, TNF-α, vascular endothelial growth factor, BMP, Wnt, apoptosis, hematopoietic stem cell self-renewal, angiogenesis, chondrogenesis, embryonic development, fibrosis, diabetic nephropathy, systemic sclerosis, cancer, therapeutic target
MeSH terms: Animals, Extracellular Matrix, Humans, Signal Transduction, CCN Intercellular Signaling Proteins

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Functions and mechanisms of action of CCN matricellular proteins

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