Nephronectin mediates p38 MAPK‐induced cell viability via its integrin‐binding enhancer motif
Jimita Toraskar,
Synnøve N. Magnussen,
Konika Chawla,
Gunbjørg Svineng,
Tonje S. Steigedal
Affiliations
Jimita Toraskar
Department of Clinical and Molecular Medicine Faculty of Medicine and Health Sciences Norwegian University of Science and Technology (NTNU) Trondheim Norway
Synnøve N. Magnussen
Department of Medical Biology Faculty of Health Sciences UiT‐The Arctic University of Norway Tromsø Norway
Konika Chawla
Department of Clinical and Molecular Medicine Faculty of Medicine and Health Sciences Norwegian University of Science and Technology (NTNU) Trondheim Norway
Gunbjørg Svineng
Department of Medical Biology Faculty of Health Sciences UiT‐The Arctic University of Norway Tromsø Norway
Tonje S. Steigedal
Department of Clinical and Molecular Medicine Faculty of Medicine and Health Sciences Norwegian University of Science and Technology (NTNU) Trondheim Norway
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.
