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

Nir Ben-Chetrit, David Chetrit, Roslin Russell, Cindy Körner, Maicol Mancini, Ali Abdul-Hai, Tomer Itkin, Silvia Carvalho, Hadas Cohen-Dvashi, Wolfgang J. Koestler, Kirti Shukla, Moshit Lindzen, Merav Kedmi, Mattia Lauriola, Ziv Shulman, Haim Barr, Dalia Seger, Daniela A. Ferraro, Fresia Pareja, Hava Gil-HennTsvee Lapidot, Ronen Alon, Ferna Milanezi, Marc Symons, Rotem Ben-Hamo, Sol Efroni, Ferno Schmitt, Stefan Wiemann, Carlos Caldas, Marcelo Ehrlich, Yosef Yarden

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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.

Original languageEnglish
Article numberra7
JournalScience Signaling
Volume8
Issue number360
DOIs
StatePublished - 20 Jan 2015

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© 2015, American Association for the Advancement of Science. All rights reserved.

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