Document Detail


Inhibition of stathmin1 accelerates the metastatic process.
MedLine Citation:
PMID:  22915755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Karin Williams; Ritwik Ghosh; Premkumar Vummidi Giridhar; Guangyu Gu; Thomas Case; Scott M Belcher; Susan Kasper
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Publication Detail:
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:
Title:  Cancer research     Volume:  72     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-16     Completed Date:  2012-12-26     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5407-17     Citation Subset:  IM    
Affiliation:
Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Cells, Cultured
DNA Primers
Down-Regulation
Humans
Male
Neoplasm Metastasis*
Signal Transduction
Stathmin / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
R01 DK059142/DK/NIDDK NIH HHS; R01 DK059142/DK/NIDDK NIH HHS; R01 DK060957/DK/NIDDK NIH HHS; R01 DK60957/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/STMN1 protein, human; 0/Stathmin
Comments/Corrections

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