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Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades.

Publication ,  Journal Article
Schiemann, WP; Blobe, GC; Kalume, DE; Pandey, A; Lodish, HF
Published in: J Biol Chem
July 26, 2002

Fibulin-5 (FBLN-5; also known as DANCE or EVEC) is an integrin-binding extracellular matrix protein that mediates endothelial cell adhesion; it is also a calcium-dependent elastin-binding protein that scaffolds cells to elastic fibers, thereby preventing elastinopathy in the skin, lung, and vasculature. Transforming growth factor-beta (TGF-beta) regulates the production of cytokines, growth factors, and extracellular matrix proteins by a variety of cell types and tissues. We show here that TGF-beta stimulates murine 3T3-L1 fibroblasts to synthesize FBLN-5 transcript and protein through a Smad3-independent pathway. Overexpression of FBLN-5 in 3T3-L1 cells increased DNA synthesis and enhanced basal and TGF-beta-stimulated activation of ERK1/ERK2 and p38 mitogen-activated protein kinase (MAPK). FBLN-5 overexpression also augmented the tumorigenicity of human HT1080 fibrosarcoma cells by increasing their DNA synthesis, migration toward fibronectin, and invasion through synthetic basement membranes. In stark contrast, FBLN-5 expression was down-regulated in the majority of metastatic human malignancies, particularly in cancers of the kidney, breast, ovary, and colon. Unlike its proliferative response in fibroblasts, FBLN-5 overexpression in mink lung Mv1Lu epithelial cells resulted in an antiproliferative response, reducing their DNA synthesis and cyclin A expression. Moreover, FBLN-5 synergizes with TGF-beta in stimulating AP-1 activity in Mv1Lu cells, an effect that was abrogated by overexpression of dominant-negative versions of either MKK1 or p38 MAPKalpha. Accordingly, both the stimulation and duration of ERK1/ERK2 and p38 MAPK by TGF-beta was enhanced in Mv1Lu cells expressing FBLN-5. Our findings identify FBLN-5 as a novel TGF-beta-inducible target gene that regulates cell growth and motility in a context-specific manner and affects protein kinase activation by TGF-beta. Our findings also indicate that aberrant FBLN-5 expression likely contributes to tumor development in humans.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 26, 2002

Volume

277

Issue

30

Start / End Page

27367 / 27377

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Tissue Distribution
  • Time Factors
  • Thymidine
  • Retroviridae
  • Recombinant Proteins
  • Plasmids
  • Neoplasm Invasiveness
  • Mitogen-Activated Protein Kinases
 

Citation

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Schiemann, W. P., Blobe, G. C., Kalume, D. E., Pandey, A., & Lodish, H. F. (2002). Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades. J Biol Chem, 277(30), 27367–27377. https://doi.org/10.1074/jbc.M200148200
Schiemann, William P., Gerard C. Blobe, Dario E. Kalume, Akhilesh Pandey, and Harvey F. Lodish. “Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades.J Biol Chem 277, no. 30 (July 26, 2002): 27367–77. https://doi.org/10.1074/jbc.M200148200.
Schiemann, William P., et al. “Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades.J Biol Chem, vol. 277, no. 30, July 2002, pp. 27367–77. Pubmed, doi:10.1074/jbc.M200148200.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 26, 2002

Volume

277

Issue

30

Start / End Page

27367 / 27377

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Tissue Distribution
  • Time Factors
  • Thymidine
  • Retroviridae
  • Recombinant Proteins
  • Plasmids
  • Neoplasm Invasiveness
  • Mitogen-Activated Protein Kinases