Abstract
Altered interactions between the extracellular matrix and cells play an important part in tumorigenesis and metastasis. As a member of a matricellular glycoprotein, fibulin-5 is expressed in elastin-rich tissues and organizes the matrix structures by interacting with many extracellular proteins. Fibulin-5 expression is closely associated with normal embryonic development and organogenesis. Mice deficient for the fibulin-5 gene exhibit systemic elastic fiber defects with manifestation of loose skin, emphysematous lungs and tortuous vessels. Additionally, fibulin-5 null mice exhibited increased angiogenesis after wound healing or PVA sponge implantation and matrigel implantation experiments show that fibulin-5 inhibits vessel formation, suggesting its function as an angiogenesis inhibitor. Fibulin-5 also plays critical roles in proliferation, migration and invasion of certain tumors, and the effect of fibulin-5 on tumorigenesis appears to be largely context-dependent. This effect might involve the inhibiting action of fibulin-5 on angiogenesis. This review focuses on recent advances in our understanding of the roles of fibulin-5 in tumorigenesis: both tumor promoting and suppressing activities of fibulin-5 are reviewed, and the emerging evidence of its promising potential for therapeutic options and/or targets in the treatment of cancer is also highlighted.
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Abbreviations
- ECM:
-
extracellular matrix
- EGF:
-
epidermal growth factor
- EMT:
-
epithelial-mesenchymal transitions
- ERK:
-
extracellular signal-regulated kinase
- LTBP-2:
-
latent TGF-β-binding protein 2
- LOXL-1:
-
lysyl oxidase-like enzyme 1
- MAPK:
-
mitogen-activated protein kinases
- MMP:
-
matrix metalloproteinase
- PDGF:
-
platelet-derived growth factor
- RGD:
-
arginine-glycine-aspartic acid
- ROS:
-
reactive oxygen species
- TGF-β:
-
transforming growth factor β
- TSP-1:
-
thrombospondin 1
- VEGF:
-
vascular endothelial growth factor
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Published in Russian in Molekulyarnaya Biologiya, 2014, Vol. 48, No. 6, pp. 875–880.
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Tang, J.C., Xie, A.Y. & Cai, X.J. Diverse functions of fibulin-5 in tumor. Mol Biol 48, 761–766 (2014). https://doi.org/10.1134/S002689331406017X
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DOI: https://doi.org/10.1134/S002689331406017X