| Autor: |
Toraskar, Jimita, Magnussen, Synnøve N., Chawla, Konika, Svineng, Gunbjørg, Steigedal, Tonje S. |
| Předmět: |
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| Zdroj: |
FEBS Open Bio; Dec2018, Vol. 8 Issue 12, p1992-2001, 10p |
| Abstrakt: |
Nephronectin (NPNT) is an extracellular matrix (ECM) protein involved in kidney development. We recently reported intracellular NPNT as a potential prognostic marker in breast cancer and that NPNT promotes metastasis in an integrin‐dependent manner. Here, we used reverse‐phase protein array (RPPA) to analyze NPNT‐triggered intracellular signaling in the 66cl4 mouse breast cancer cell line. The results showed that the integrin‐binding enhancer motif is important for the cellular effects upon NPNT interaction with its receptors, including phosphorylation of p38 mitogen‐activated protein kinase (MAPK). Furthermore, analysis using prediction tools suggests involvement of NPNT in promoting cell viability. In conclusion, our results indicate that NPNT, via its integrin‐binding motifs, promotes cell viability through phosphorylation of p38 MAPK. Extracellular nephronectin is known to interact with transmembrane integrin receptors. We found that the nephronectin–integrin interaction augments overall cell viability via phosphorylation of p38 MAPK. Disrupting the integrin binding sites of nephronectin or inhibiting phosphorylation of p38 MAPK hindered cell viability. These findings suggest a potential drug target in tumors with high nephronectin expression. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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