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Diverse functions of fibulin-5 in tumor

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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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Authors and Affiliations

  1. Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, P. R. China

    J. -C. Tang, A. -Y. Xie & X. -J. Cai

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  1. J. -C. Tang
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  2. A. -Y. Xie
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  3. X. -J. Cai
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Correspondence to X. -J. Cai.

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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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