Synaptojanin 2 is a druggable mediator of metastasis and the gene is overexpressed and amplified in breast cancer
Publication Date
2015
Journal Title
Sci Signal
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.
Volume Number
8
Issue Number
360
Pages
13
Document Type
Article
EPub Date
2015/01/22
Status
Faculty
Facility
School of Medicine
Primary Department
Molecular Medicine
Additional Departments
Neurosurgery
PMID
DOI
10.1126/scisignal.2005537
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