Abstract
The protein tyrosine phosphatase receptor PTPRN2 is expressed predominantly in endocrine and neuronal cells, where it functions in exocytosis. We found that its immature isoform proPTPRN2 is overexpressed in various cancers, including breast cancer. High proPTPRN2 expression was associated strongly with lymph node-positive breast cancer and poor clinical outcome. Loss of proPTPRN2 in breast cancer cells promoted apoptosis and blocked tumor formation in mice, whereas enforced expression of proPTPRN2 in nontransformed human mammary epithelial cells exerted a converse effect. Mechanistic investigations suggested that ProPTPRN2 elicited these effects through direct interaction with TRAF2, a hub scaffold protein for multiple kinase cascades, including ones that activate NF-κB. Overall, our results suggest PTPRN2 as a novel candidate biomarker and therapeutic target in breast cancer.
©2015 American Association for Cancer Research.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Line
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Cell Line, Tumor
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Female
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HCT116 Cells
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HEK293 Cells
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HeLa Cells
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Heterografts
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Humans
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Lymph Nodes / metabolism
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Lymph Nodes / pathology
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Lymphatic Metastasis
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MCF-7 Cells
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Mammary Glands, Human / metabolism
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Mammary Glands, Human / pathology
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Mice
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Mice, Inbred BALB C
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Neoplasms / genetics
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Neoplasms / metabolism*
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Neoplasms / pathology*
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Receptor-Like Protein Tyrosine Phosphatases, Class 8 / biosynthesis*
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Receptor-Like Protein Tyrosine Phosphatases, Class 8 / genetics
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Receptor-Like Protein Tyrosine Phosphatases, Class 8 / metabolism
Substances
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NF-kappa B
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PTPRN2 protein, human
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Receptor-Like Protein Tyrosine Phosphatases, Class 8