Research ArticleCancer

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

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Science Signaling  20 Jan 2015:
Vol. 8, Issue 360, pp. ra7
DOI: 10.1126/scisignal.2005537

Blocking Receptor Recycling to Prevent Metastasis

Blocking cancer cell metastasis can prolong patient survival. Ben-Chetrit et al. found that many patients with aggressive breast cancer have tumors with increased expression of SYNJ2, which encodes the lipid phosphatase synaptojanin 2. In cultured breast cancer cells, epidermal growth factor (EGF) triggered the localization of SYNJ2 to lamellipodia and invadopodia, which are cellular protrusions associated with invasive behavior. Knocking down SYNJ2 inhibited recycling of the EGF receptor to the cell surface and decreased the invasive behavior of cultured breast cancer cells. Expressing a phosphatase-deficient mutant of SYNJ2 in xenografted breast cancer cells suppressed tumor growth and lung metastasis in mice. A chemical screen identified SYNJ2 inhibitors that reduced cell invasion through a 3D matrix, suggesting that targeting SYNJ2 may prevent metastasis in breast cancer patients.

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