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

Merav Kedmi, Nir Ben-Chetrit, Cindy Körner, Maicol Mancini, Noa Bossel Ben-Moshe, Mattia Lauriola, Sara Lavi, Francesca Biagioni, Silvia Carvalho, Hadas Cohen-Dvashi, Fernando Schmitt, Stefan Wiemann, Giovanni Blandino, Yosef Yarden

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)ra29
JournalScience Signaling
Volume8
Issue number368
DOIs
Publication statusPublished - Mar 17 2015

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Tumor Suppressor Proteins
MicroRNAs
Epidermal Growth Factor
Cell Movement
Breast Neoplasms
Tumors
Intercellular Signaling Peptides and Proteins
Breast
Tissue
Neoplasms
Stress Fibers
3' Untranslated Regions
Growth
Heterografts
Actins
Epithelial Cells
Cells
Neoplasm Metastasis
Cell Line
Fibers

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Kedmi, M., Ben-Chetrit, N., Körner, C., Mancini, M., Ben-Moshe, N. B., Lauriola, M., ... Yarden, Y. (2015). EGF induces microRNAs that target suppressors of cell migration: MiR-15b targets MTSS1 in breast cancer. Science Signaling, 8(368), ra29. https://doi.org/10.1126/scisignal.2005866

EGF induces microRNAs that target suppressors of cell migration : MiR-15b targets MTSS1 in breast cancer. / Kedmi, Merav; Ben-Chetrit, Nir; Körner, Cindy; Mancini, Maicol; Ben-Moshe, Noa Bossel; Lauriola, Mattia; Lavi, Sara; Biagioni, Francesca; Carvalho, Silvia; Cohen-Dvashi, Hadas; Schmitt, Fernando; Wiemann, Stefan; Blandino, Giovanni; Yarden, Yosef.

In: Science Signaling, Vol. 8, No. 368, 17.03.2015, p. ra29.

Research output: Contribution to journalArticle

Kedmi, M, Ben-Chetrit, N, Körner, C, Mancini, M, Ben-Moshe, NB, Lauriola, M, Lavi, S, Biagioni, F, Carvalho, S, Cohen-Dvashi, H, Schmitt, F, Wiemann, S, Blandino, G & Yarden, Y 2015, 'EGF induces microRNAs that target suppressors of cell migration: MiR-15b targets MTSS1 in breast cancer', Science Signaling, vol. 8, no. 368, pp. ra29. https://doi.org/10.1126/scisignal.2005866
Kedmi, Merav ; Ben-Chetrit, Nir ; Körner, Cindy ; Mancini, Maicol ; Ben-Moshe, Noa Bossel ; Lauriola, Mattia ; Lavi, Sara ; Biagioni, Francesca ; Carvalho, Silvia ; Cohen-Dvashi, Hadas ; Schmitt, Fernando ; Wiemann, Stefan ; Blandino, Giovanni ; Yarden, Yosef. / EGF induces microRNAs that target suppressors of cell migration : MiR-15b targets MTSS1 in breast cancer. In: Science Signaling. 2015 ; Vol. 8, No. 368. pp. ra29.
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