The Effects of Recombinant Synucleins and Insulin-like Growth Factor 1 on Cancer Cell Migration The Effects of Recombinant Synucleins and Insulin-like Growth Factor 1 on Cancer Cell Migration

Abstract

The synuclein family consists of three distinct genes, α-synuclein, β-synuclein, and γ-synuclein. The α-synuclein and β-synuclein are predominately expressed in brain and especially α-synuclein is related with Parkinson's disease, Alzheimer's disease, and dementia with Lewy bodies. The γ-synuclein was first identified as breast cancer specific gene 1. It is expressed in the peripheral nervous system and also detected in breast and ovarian cancers. The γ-synuclein is also known to mediate metastasis of breast and ovarian cancer cells. Insulin-like growth factor 1 (IGF-I) is one of the growth factors that plays an important role in cell proliferation and migration in cancer cells, as well as in normal cells. In this study, we investigated the migrations of SKOV-3, MDAMB-231, and HeLa cells by the recombinant synuclein proteins (α-, β-, and γ-synucleins) and IGF-I and the molecular mechanism. Furthermore, we investigated the membrane ruffle formation of SKOV-3 cells by recombinant synuclein proteins and IGF-I. As a result, synucleins and IGF-I were found to induce cancer cell migrations. Simultaneous synucleins and IGF-I treatment on the cancer cells induced more migrations than the individual synuclein or IGF-I treatments. The synucleins or IGF-I treatments increased the expressions of membrane-type1 matrix metalloproteinase (MT1-MMP) and cluster of differentiation 44 (CD44). Moreover, simultaneous synucleins and IGF-I treatments further increased the expressions of MT1-MMP and CD44. The synucleins and IGF-I promoted the conformational change of actin filaments, and then this led to the membrane ruffle formation.