In our studies, hRNase 1 as a natively secretory protein freely circulating in various body fluids, e.g., serum and plasma, is demonstrated as a ligand of EphA4 receptor that enhances breast cancer stem-like properties, namely that hRNase 1-mediated EphA4 activation is mainly through an autocrine/paracrine mechanism. The gene discussed is EPHA4; the disease is breast cancer.