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Matricellular protein CCN3 (NOV) regulates actin cytoskeleton reorganization.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2009 Oct 23; Vol. 284 (43), pp. 29935-44. Date of Electronic Publication: 2009 Aug 25. - Publication Year :
- 2009
-
Abstract
- CCN3 (NOV), a putative ligand for integrin receptors, is tightly associated with the extracellular matrix and mediates diverse cellular functions, including cell adhesion and proliferation. CCN3 has been shown to negatively regulate growth although it promotes migration in a cell type-specific manner. In this study, overexpression of CCN3 reduces growth and increases intercellular adhesion of breast cancer cells. Interestingly, CCN3 overexpression also led to the formation of multiple pseudopodia that are enriched in actin, CCN3, and vinculin. Breast cancer cells preincubated with exogenous CCN3 protein also induced the same phenotype, indicating that secreted CCN3 is sufficient to induce changes in cell morphology. Surprisingly, extracellular CCN3 is internalized to the early endosomes but not to the membrane protrusions, suggesting pseudopodia-enriched CCN3 may derive from a different source. The presence of an intracellular variant of CCN3 will be consistent with our finding that the cytoplasmic tail of the gap junction protein connexin43 (Cx43) associates with CCN3. Cx43 is a channel protein permitting intercellular communication to occur. However, neither the channel properties nor the protein levels of Cx43 are affected by the CCN3 protein. In contrast, CCN3 proteins are down-regulated in the absence of Cx43. Finally, we showed that overexpression of CCN3 increases the activity of the small GTPase Rac1, thereby revealing a pathway that links Cx43 directly to actin reorganization.
- Subjects :
- Actins genetics
Breast Neoplasms genetics
Cell Adhesion genetics
Cell Line, Tumor
Connexin 43 genetics
Cytoskeleton genetics
Down-Regulation genetics
Gene Expression Regulation, Neoplastic genetics
Humans
Male
Neoplasm Proteins genetics
Nephroblastoma Overexpressed Protein genetics
Pseudopodia genetics
Pseudopodia metabolism
rac1 GTP-Binding Protein genetics
rac1 GTP-Binding Protein metabolism
Actins metabolism
Breast Neoplasms metabolism
Connexin 43 metabolism
Cytoskeleton metabolism
Neoplasm Proteins metabolism
Nephroblastoma Overexpressed Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 284
- Issue :
- 43
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 19706598
- Full Text :
- https://doi.org/10.1074/jbc.M109.042630