EGF induces microRNAs that target suppressors of cell migration: MiR-15b targets MTSS1 in breast cancer

Growth factors promote tumor growth and metastasis. We found that epidermal growth factor (EGF) induced a set of 22 microRNAs (miRNAs) before promoting the migration of mammary cells. These miRNAs were more abundant in human breast tumors relative to the surrounding tissue, and their abundance varied among breast cancer subtypes. One of these miRNAs, miR-15b, targeted the 3′ untranslated region of MTSS1 (metastasis suppressor protein 1). Although xenografts in which MTSS1 was knocked down grew more slowly in mice initially, longer-term growth was unaffected. Knocking down MTSS1 increased migration and Matrigel invasion of nontransformed mammary epithelial cells. Overexpressing MTSS1 in an invasive cell line decreased cellmigration and invasiveness, decreased the formation of invadopodia and actin stress fibers, and increased the formation of cellular junctions. In tissues frombreast cancer patientswith the aggressive basal subtype, an inverse correlation occurred with the high expression of miRNA-15b and the low expression of MTSS1. Further more, low abundance of MTSS1 correlated with poor patient prognosis. Thus, growth factor.inducible miRNAs mediate mechanisms underlying the progression of cancer.