Publication: The CCN proteins: important signaling mediators
in stem cell differentiation and tumorigenesis
Authors
Zuo, Guo-Wei ; Kohls, Christopher D. ; He, Bai-Cheng ; Chen, Liang ; Zhang, Wenli ; Shi, Qiong ; Zhang, Bing-Qiang ; Kang, Quan ; Luo, Jinyong ; Luo, Xiaoji ; Wagner, Eric R. ; Kim, Stephanie H. ; Restegar, Farbod ; Haydon, Rex C. ; Deng, Zhong-Liang ; Luu, Hue H. ; He, Tong-Chuan ; Luo, Qing
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Publisher
Murcia: F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The CCN proteins contain six members,
namely CCN1 to CCN6, which are small secreted
cysteine-rich proteins. The CCN proteins are modular
proteins, containing up to four functional domains.
Many of the CCN members are induced by growth
factors, cytokines, or cellular stress. The CCNs show a
wide and highly variable expression pattern in adult and
in embryonic tissues. The CCN proteins can integrate
and modulate the signals of integrins, BMPs, VEGF,
Wnts, and Notch. The involvement of integrins in
mediating CCN signaling may provide diverse contextdependent
responses in distinct cell types. CCN1 and
CCN2 play an important role in development,
angiogenesis and cell adhesion, whereas CCN3 is critical
to skeletal and cardiac development. CCN4, CCN5 and
CCN6 usually inhibit cell growth. Mutations of Ccn6 are
associated with the progressive pseudorheumatoid
dysplasia and spondyloepiphyseal dysplasia tarda. In
stem cell differentiation, CCN1, CCN2, and CCN3 play
a principal role in osteogenesis, chondrogenesis, and
angiogenesis. Elevated expression of CCN1 is associated
with more aggressive phenotypes of human cancer,
while the roles of CCN2 and CCN3 in tumorigenesis are
tumor type-dependent. CCN4, CCN5 and CCN6
function as tumor suppressors. Although CCN proteins
may play important roles in fine-tuning other major signaling pathways, the precise function and mechanism
of action of these proteins remain undefined.
Understanding of the biological functions of the CCN
proteins would not only provide insight into their roles
in numerous cellular processes but also offer
opportunities for developing therapeutics by targeting
CCN functions.
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