title: EGF induces microRNAs that target suppressors of cell migration: miR-15b targets MTSS1 in breast cancer.
abstract: 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 cell migration and invasiveness, decreased the formation of invadopodia and actin stress fibers, and increased the formation of cellular junctions. In tissues from breast cancer patients with the aggressive basal subtype, an inverse correlation occurred with the high expression of miRNA-15b and the low expression of MTSS1. Furthermore, low abundance of MTSS1 correlated with poor patient prognosis. Thus, growth factor-inducible miRNAs mediate mechanisms underlying the progression of cancer.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Kedmi
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Ben-Chetrit
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
authors.forename: Cindy
authors.initials: C
authors.lastname: Körner
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Maicol
authors.initials: M
authors.lastname: Mancini
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Noa Bossel
authors.initials: NB
authors.lastname: Ben-Moshe
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Mattia
authors.initials: M
authors.lastname: Lauriola
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Lavi
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute "Regina Elena," Rome 00144, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Biagioni
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Silvia
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Cohen-Dvashi
authors.affiliation: Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto and Department of Pathology, University Health Network, Toronto, Ontario M5C 2C4, Canada. IPATIMUP, University of Porto, Porto 4200-465, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiemann
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute "Regina Elena," Rome 00144, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. yosef.yarden@weizmann.ac.il.
authors.forename: Yosef
authors.initials: Y
authors.lastname: Yarden
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation
chemical_list: C505361:MIRN15 microRNA, human; C486778:MTSS1 protein, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D004815:Epidermal Growth Factor