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Synaptojanin 2 is a druggable mediator of metastasis and the gene is overexpressed and amplified in breast cancer

Authors :
Ronen Alon
Hava Gil-Henn
Rotem Ben-Hamo
Marcelo Ehrlich
Nir Ben-Chetrit
Yosef Yarden
Tomer Itkin
Wolfgang J. Koestler
Dalia Seger
Silvia Carvalho
Carlos Caldas
Maicol Mancini
Ali Abdul-Hai
Daniela Aleida Ferraro
David Chetrit
Fresia Pareja
Mattia Lauriola
Marc Symons
Kirti Shukla
Ziv Shulman
Tsvee Lapidot
Hadas Cohen-Dvashi
Cindy Körner
Fernanda Milanezi
Moshit Lindzen
Merav Kedmi
Fernando Schmitt
Stefan Wiemann
Haim Barr
Sol Efroni
Roslin Russell
Ben-Chetrit, Nir
Chetrit, David
Russell, Roslin
K('o)rner, Cindy
Mancini, Maicol
Abdul-Hai, Ali
Itkin, Tomer
Carvalho, Silvia
Cohen-Dvashi, Hada
Koestler, Wolfgang J.
Shukla, Kirti
Lindzen, Moshit
Kedmi, Merav
Lauriola, Mattia
Shulman, Ziv
Barr, Haim
Seger, Dalia
Ferraro, Daniela A.
Pareja, Fresia
Gil-Henn, Hava
Lapidot, Tsvee
Alon, Ronen
Milanezi, Fernanda
Symons, Marc
Ben-Hamo, Rotem
Efroni, Sol
Schmitt, Fernando
Wiemann, Stefan
Caldas, Carlo
Ehrlich, Marcelo
Yarden, Yosef
Source :
Science signaling. 8(360)
Publication Year :
2015

Abstract

Amplified HER2, which encodes a member of the epidermal growth factor receptor (EGFR) family, is a target of effective therapies against breast cancer. In search for similarly targetable genomic aberrations, we identified copy number gains in SYNJ2, which encodes the 5'-inositol lipid phosphatase synaptojanin 2, as well as overexpression in a small fraction of human breast tumors. Copy gain and overexpression correlated with shorter patient survival and a low abundance of the tumor suppressor microRNA miR-31. SYNJ2 promoted cell migration and invasion in culture and lung metastasis of breast tumor xenografts in mice. Knocking down SYNJ2 impaired the endocytic recycling of EGFR and the formation of cellular lamellipodia and invadopodia. Screening compound libraries identified SYNJ2-specific inhibitors that prevented cell migration but did not affect the related neural protein SYNJ1, suggesting that SYNJ2 is a potentially druggable target to block cancer cell migration.

Details

ISSN :
19379145
Volume :
8
Issue :
360
Database :
OpenAIRE
Journal :
Science signaling
Accession number :
edsair.doi.dedup.....9113dd552e1aaea3dcf991b34e80777b