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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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Periostin-binding DNA Aptamer Inhibits Breast Cancer Growth and Metastasis

Cited 7 times inthomson ciCited 7 times inthomson ci
Title
Periostin-binding DNA Aptamer Inhibits Breast Cancer Growth and Metastasis
Author
Lee, Yu JinKim, Il ShinPark, Soo-AhKim, YoundongLee, Jeung EunNoh, Dong-YoungKim, Kyong-TaiRyu, Sung HoSuh, Pann-Ghill
Keywords
CELL-SURVIVAL; EXPONENTIAL ENRICHMENT; SYSTEMATIC EVOLUTION; BONE METASTASES; AKT/PKB PATHWAY; TUMOR-GROWTH; LUNG-CANCER; TENASCIN-C; EXPRESSION; ANTIBODY
Issue Date
201305
Publisher
NATURE PUBLISHING GROUP
Citation
MOLECULAR THERAPY, v.21, no.5, pp.1004 - 1013
Abstract
Periostin is an extracellular matrix (ECM) protein that is overexpressed in a variety of human cancers, and its functions appear to be linked to tumor growth, metastasis, and angiogenesis. Recent clinical evidence suggests that aberrant periostin expression is correlated with poor outcome in patients with breast cancer. To identify novel tools to regulate the functional role of periostin, we generated benzyl-d(U)TP-modified DNA aptamers that were directed against human periostin (PNDAs) and characterized their functional roles in breast cancer progression. PNDA-3 selectively bound to the FAS-1 domain of periostin with nanomolar affinity and disrupted the interaction between periostin and its cell surface receptors, alpha(v)beta(3) and alpha(v)beta(5) integrins. PNDA-3 markedly antagonized the periostin-induced adhesion, migration, and invasion of breast cancer cells and blocked the activation of various components of the alpha(v)beta(3) and alpha(v)beta(5) integrin signal transduction pathways. In a 4T1 orthotopic mouse model, PNDA-3 administration significantly reduced primary tumor growth and distant metastasis. Thus, our results demonstrated that periostin-integrin signaling regulates breast cancer progression at multiple levels in tumor cells and the tumor microenvironment. DNA aptamers targeting periostin may potentially be used to inhibit breast cancer progression.
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DOI
http://dx.doi.org/10.1038/mt.2013.30
ISSN
1525-0016
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