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

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Kedmi, M (Author) Other; Ben Chetrit, N (Author) Other; Koerner, C (Author) Other; Mancini, M (Author) Other; Ben Moshe, NB (Author) Other; Lauriola, M (Author) Other; Lavi, S (Author) Other; Biagioni, F (Author) Other; Carvalho, S (Author) Other; Cohen Dvashi, H (Author) Other; Fernando Schmitt (Author) FMUP; Wiemann, S (Author) Other; Blandino, G (Author) Other; Yarden, Y (Author) Other

Journal

Title: Science Signaling

Vol. 8

Final page: ra29

ISSN: 1945-0877

Publisher: American Association for the Advancement of Science

Indexing

ISI Web of Knowledge - 55 Citations

Scopus - 56 Citations

Other information

Authenticus ID: P-00A-9WZ

DOI: 10.1126/scisignal.2005866

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12