Micromanaging growth factor–induced metastasis
Epidermal growth factor (EGF) stimulates cell proliferation and tumor growth in part by triggering kinase-dependent changes in gene expression. Noncoding RNAs, such as microRNAs (miRNAs), reduce gene expression by binding to protein-encoding transcripts. Kedmi et al. found that EGF stimulated migration in mammary epithelial cells and also increased the abundance of a set of miRNAs. Of these, miR-15b promoted EGF-induced migration and reduced the abundance of metastasis suppressor protein 1 (MTSS1). The expression of miR-15b was higher in aggressive tumors than in adjacent normal tissue and inversely correlated with that of MTSS1. Knockdown of MTSS1 promoted the migratory behavior and the formation of migration-associated structures in cultured cells. Low abundance of MTSS1 correlated with shorter survival in patients, and low expression of MTSS1 correlated with high expression of miR-15b in aggressive basal breast cancer tissue, suggesting that this pathway is important in breast cancer and could be targeted to reduce metastatic disease in patients.
