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

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

Science signaling (2015-01-22)
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
RESUMO

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.

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Sigma-Aldrich
Fluorescein 5(6)-isothiocyanate, BioReagent, suitable for fluorescence, mixture of 2 components, ≥90% (HPLC)
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Fluorescein isothiocyanate isomer I, suitable for protein labeling, ≥90% (HPLC), powder
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Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)