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SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane.

Publication ,  Journal Article
Morrissey, MA; Jayadev, R; Miley, GR; Blebea, CA; Chi, Q; Ihara, S; Sherwood, DR
Published in: PLoS genetics
February 2016

Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments. Using the model of anchor cell invasion through the basement membrane (BM) extracellular matrix in Caenorhabditis elegans, we find that SPARC overexpression is highly pro-invasive and rescues BM transmigration in mutants with defects in diverse aspects of invasion, including cell polarity, invadopodia formation, and matrix metalloproteinase expression. By examining BM assembly, we find that overexpression of SPARC specifically decreases levels of BM type IV collagen, a crucial structural BM component. Reduction of type IV collagen mimicked SPARC overexpression and was sufficient to promote invasion. Tissue-specific overexpression and photobleaching experiments revealed that SPARC acts extracellularly to inhibit collagen incorporation into BM. By reducing endogenous SPARC, we also found that SPARC functions normally to traffic collagen from its site of synthesis to tissues that do not express collagen. We propose that a surplus of SPARC disrupts extracellular collagen trafficking and reduces BM collagen incorporation, thus weakening the BM barrier and dramatically enhancing its ability to be breached by invasive cells.

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Published In

PLoS genetics

DOI

EISSN

1553-7404

ISSN

1553-7390

Publication Date

February 2016

Volume

12

Issue

2

Start / End Page

e1005905

Related Subject Headings

  • Proto-Oncogene Proteins c-fos
  • Osteonectin
  • Mutation
  • Gene Expression Regulation
  • Extracellular Matrix
  • Developmental Biology
  • Collagen Type IV
  • Caenorhabditis elegans Proteins
  • Caenorhabditis elegans
  • Basement Membrane
 

Citation

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ICMJE
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Morrissey, M. A., Jayadev, R., Miley, G. R., Blebea, C. A., Chi, Q., Ihara, S., & Sherwood, D. R. (2016). SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane. PLoS Genetics, 12(2), e1005905. https://doi.org/10.1371/journal.pgen.1005905
Morrissey, Meghan A., Ranjay Jayadev, Ginger R. Miley, Catherine A. Blebea, Qiuyi Chi, Shinji Ihara, and David R. Sherwood. “SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane.PLoS Genetics 12, no. 2 (February 2016): e1005905. https://doi.org/10.1371/journal.pgen.1005905.
Morrissey MA, Jayadev R, Miley GR, Blebea CA, Chi Q, Ihara S, et al. SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane. PLoS genetics. 2016 Feb;12(2):e1005905.
Morrissey, Meghan A., et al. “SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane.PLoS Genetics, vol. 12, no. 2, Feb. 2016, p. e1005905. Epmc, doi:10.1371/journal.pgen.1005905.
Morrissey MA, Jayadev R, Miley GR, Blebea CA, Chi Q, Ihara S, Sherwood DR. SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane. PLoS genetics. 2016 Feb;12(2):e1005905.

Published In

PLoS genetics

DOI

EISSN

1553-7404

ISSN

1553-7390

Publication Date

February 2016

Volume

12

Issue

2

Start / End Page

e1005905

Related Subject Headings

  • Proto-Oncogene Proteins c-fos
  • Osteonectin
  • Mutation
  • Gene Expression Regulation
  • Extracellular Matrix
  • Developmental Biology
  • Collagen Type IV
  • Caenorhabditis elegans Proteins
  • Caenorhabditis elegans
  • Basement Membrane