Nephronectin mediates p38 MAPK-induced cell viability via its integrin-binding enhancer motif

FEBS Open Bio. 2018 Nov 15;8(12):1992-2001. doi: 10.1002/2211-5463.12544. eCollection 2018 Dec.

Abstract

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.

Keywords: breast cancer; cell viability; extracellular matrix; integrin; nephronectin; p38 MAPK.