| Inhibition of stathmin1 accelerates the metastatic process. | |
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MedLine Citation:
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PMID: 22915755 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The oncoprotein stathmin 1 (STMN1) is upregulated in most, if not all, cancers of epithelial cell origin; therefore STMN1 is considered a target for cancer therapy. However, its role during metastasis has not been investigated. Here, we report for the first time that STMN1 strongly inhibits metastatic behavior in both normal epithelial and cancerous epithelial cells. Initially, loss-of-STMN1 compromises cell-cell adhesion. This is followed by epithelial-to-mesenchymal transition (EMT), increased cell migration, and metastasis via cooperative activation of p38 and through TGF-β-independent and -dependent mechanisms. In contrast, expressing STMN1 restores cell-cell adhesion and reverses the metastatic cascade. Primary prostate epithelial cell cultures from benign to undifferentiated adenocarcinoma (UA) clinical biopsies show that EMT-like cells arise while the cancer is still organ-confined and that their emergence is tumor-stage specific. Furthermore, primary EMT-like cells exhibit metastatic behavior both in vitro and in vivo as compared with their non-EMT counterpart. These observations predict that using STMN1 as a generic therapeutic target might accelerate metastasis. Instead, there may be a tumor stage-specific window-of-opportunity in which conserving STMN1 expression is required to inhibit emergence of metastatic disease. |
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Authors:
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Karin Williams; Ritwik Ghosh; Premkumar Vummidi Giridhar; Guangyu Gu; Thomas Case; Scott M Belcher; Susan Kasper |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-08-21 |
Journal Detail:
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Title: Cancer research Volume: 72 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-16 Completed Date: 2012-12-26 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 5407-17 Citation Subset: IM |
Affiliation:
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Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Base Sequence Cells, Cultured DNA Primers Down-Regulation Humans Male Neoplasm Metastasis* Signal Transduction Stathmin / antagonists & inhibitors* |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK059142/DK/NIDDK NIH HHS; R01 DK60957/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/STMN1 protein, human; 0/Stathmin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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