Reference - Detail
| RRC ID | 53474 |
|---|---|
| Author | Morrissey MA, Jayadev R, Miley GR, Blebea CA, Chi Q, Ihara S, Sherwood DR. |
| Title | SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane. |
| Journal | PLoS Genet |
| Abstract |
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. |
| Volume | 12(2) |
| Pages | e1005905 |
| Published | 2016-2-1 |
| DOI | 10.1371/journal.pgen.1005905 |
| PII | PGENETICS-D-15-02743 |
| PMID | 26926673 |
| PMC | PMC4771172 |
| MeSH | Animals Animals, Genetically Modified Basement Membrane Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Collagen Type IV / metabolism* Extracellular Matrix / metabolism Gene Expression Regulation Mutation Osteonectin / genetics Osteonectin / metabolism* Proto-Oncogene Proteins c-fos / genetics |
| IF | 5.175 |
| Times Cited | 33 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 9 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm966 tm6331 |