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Sci Signal. 2015 Jan 20;8(360):ra7. doi: 10.1126/scisignal.2005537.

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

Author information

1
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
2
Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
3
Department of Oncology and Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
4
Division of Molecular Genome Analysis, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany.
5
Kaplan Medical Center, Rehovot 76100, Israel.
6
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
7
INCPM, Weizmann Institute of Science, Rehovot 76100, Israel.
8
Faculty of Medicine, Bar-Ilan University, Safed 13115, Israel.
9
IPATIMUP, University of Porto, Porto 4200-465, Portugal.
10
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
11
The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan 52900, Israel.
12
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. yosef.yarden@weizmann.ac.il.

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.

PMID:
25605973
DOI:
10.1126/scisignal.2005537
[Indexed for MEDLINE]

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