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

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Ben Chetrit, N (Author) Other; Chetrit, D (Author) Other; Russell, R (Author) Other; Koerner, C (Author) Other; Mancini, M (Author) Other; Abdul Hai, A (Author) Other; Itkin, T (Author) Other; Carvalho, S (Author) Other; Cohen Dvashi, H (Author) Other; Koestler, WJ (Author) Other; Shukla, K (Author) Other; Lindzen, M (Author) Other; Kedmi, M (Author) Other; Lauriola, M (Author) Other; Shulman, Z (Author) Other; Barr, H (Author) Other; Seger, D (Author) Other; Ferraro, DA (Author) Other; Pareja, F (Author) Other; Gil Henn, H (Author) Other; Lapidot, T (Author) Other; Alon, R (Author) Other; Milanezi, F (Author) Other; Symons, M (Author) Other; Ben Hamo, R (Author) Other; Efroni, S (Author) Other; Fernando Schmitt (Author) FMUP; Wiemann, S (Author) Other; Caldas, C (Author) Other; Ehrlich, M (Author) Other; Yarden, Y (Author) Other

Journal

Title: Science Signaling

Vol. 8

Pages: ra7-ra7

ISSN: 1945-0877

Publisher: American Association for the Advancement of Science

Indexing

ISI Web of Knowledge - 48 Citations

Scopus - 50 Citations

Other information

Authenticus ID: P-00A-4BR

DOI: 10.1126/scisignal.2005537

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13