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 language | English |
|---|---|
| Pages (from-to) | ra29 |
| Journal | Science Signaling |
| Volume | 8 |
| Issue number | 368 |
| DOIs | |
| Publication status | Published - Mar 17 2015 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - EGF induces microRNAs that target suppressors of cell migration
T2 - MiR-15b targets MTSS1 in breast cancer
AU - Kedmi, Merav
AU - Ben-Chetrit, Nir
AU - Körner, Cindy
AU - Mancini, Maicol
AU - Ben-Moshe, Noa Bossel
AU - Lauriola, Mattia
AU - Lavi, Sara
AU - Biagioni, Francesca
AU - Carvalho, Silvia
AU - Cohen-Dvashi, Hadas
AU - Schmitt, Fernando
AU - Wiemann, Stefan
AU - Blandino, Giovanni
AU - Yarden, Yosef
PY - 2015/3/17
Y1 - 2015/3/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84924961818&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924961818&partnerID=8YFLogxK
U2 - 10.1126/scisignal.2005866
DO - 10.1126/scisignal.2005866
M3 - Article
C2 - 25783158
AN - SCOPUS:84924961818
VL - 8
SP - ra29
JO - Science Signaling
JF - Science Signaling
SN - 1937-9145
IS - 368
ER -