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-Henn; Tsvee Lapidot; Ronen Alon; Fernanda Milanezi; Marc Symons; Rotem Ben-Hamo; Sol Efroni; Fernando Schmitt; Stefan Wiemann; Carlos Caldas; Marcelo Ehrlich; Yosef Yarden

doi:10.1126/scisignal.2005537

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

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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, …

Science signaling, Vol.8(360), pp.ra7-ra7

20/01/2015

DOI: https://doi.org/10.1126/scisignal.2005537

PMID: 25605973

Résumé

Animals

Breast Neoplasms - drug therapy

Breast Neoplasms - genetics

Breast Neoplasms - metabolism

Breast Neoplasms - physiopathology

Cell Line, Tumor

Cell Movement - drug effects

Drug Discovery

ErbB Receptors - metabolism

Female

Fluorescent Antibody Technique

Gene Dosage

Gene Expression Regulation, Neoplastic - genetics

Humans

Image Processing, Computer-Assisted

Immunoblotting

Immunohistochemistry

Mice

Mice, SCID

Microscopy, Electron, Scanning

Neoplasm Metastasis - genetics

Phosphoric Monoester Hydrolases - antagonists & inhibitors

Phosphoric Monoester Hydrolases - genetics

Phosphoric Monoester Hydrolases - metabolism

Podosomes - genetics

Podosomes - physiology

Pseudopodia - genetics

Pseudopodia - physiology

RNA, Small Interfering - genetics

Statistics, Nonparametric

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.

Indicateurs

1 Consultations de la notice

Détails

Titre: Synaptojanin 2 is a druggable mediator of metastasis and the gene is overexpressed and amplified in breast cancer
Créateurs - sans rôle: Nir Ben-Chetrit - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
David Chetrit - Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
Roslin Russell - Department of Oncology and Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK
Cindy Körner - Division of Molecular Genome Analysis, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany
Maicol Mancini - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Ali Abdul-Hai - Kaplan Medical Center
Tomer Itkin - Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Silvia Carvalho - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Hadas Cohen-Dvashi - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Wolfgang J Koestler - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Kirti Shukla - Division of Molecular Genome Analysis, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany
Moshit Lindzen - Weizmann Institute of Science
Merav Kedmi - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Mattia Lauriola - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Ziv Shulman - Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Haim Barr - INCPM, Weizmann Institute of Science, Rehovot 76100, Israel
Dalia Seger - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Daniela A Ferraro - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Fresia Pareja - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Hava Gil-Henn - Faculty of Medicine, Bar-Ilan University, Safed 13115, Israel
Tsvee Lapidot - Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Ronen Alon - Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Fernanda Milanezi - IPATIMUP, University of Porto, Porto 4200-465, Portugal
Marc Symons - Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA
Rotem Ben-Hamo - The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan 52900, Israel
Sol Efroni - The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan 52900, Israel
Fernando Schmitt - IPATIMUP, University of Porto, Porto 4200-465, Portugal
Stefan Wiemann - Division of Molecular Genome Analysis, German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany
Carlos Caldas - University of Cambridge
Marcelo Ehrlich - Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
Yosef Yarden - Weizmann Institute of Science
Détails de publication: Science signaling, Vol.8(360), pp.ra7-ra7
Note de subvention: 16942 / Cancer Research UK
Identifiants: 99162915109311
Unité académique: Institut de Recherche en Cancérologie de Montpellier - IRCM
Langue: English
Type de ressource: Journal article