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Synaptojanin 2 is a druggable mediator of metastasis and the gene is overexpressed and amplified in breast cancer
- Source :
- Science signaling. 8(360)
- Publication Year :
- 2015
-
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.
- Subjects :
- Immunoblotting
Gene Dosage
Endocytic recycling
Fluorescent Antibody Technique
Breast Neoplasms
Synaptojanin
Mice, SCID
Biochemistry
Statistics, Nonparametric
Metastasis
Mice
Breast cancer
Growth factor receptor
BREAST CANCER
Cell Movement
Cell Line, Tumor
Drug Discovery
medicine
Image Processing, Computer-Assisted
Animals
Humans
Epidermal growth factor receptor
EGFR pathway
Pseudopodia
Neoplasm Metastasis
RNA, Small Interfering
Molecular Biology
biology
Cell migration
Cell Biology
medicine.disease
Immunohistochemistry
Phosphoric Monoester Hydrolases
ErbB Receptors
Gene Expression Regulation, Neoplastic
Immunology
Invadopodia
METASTASIS
Podosomes
Cancer research
biology.protein
Microscopy, Electron, Scanning
Female
Subjects
Details
- ISSN :
- 19379145
- Volume :
- 8
- Issue :
- 360
- Database :
- OpenAIRE
- Journal :
- Science signaling
- Accession number :
- edsair.doi.dedup.....9113dd552e1aaea3dcf991b34e80777b