Document Detail


RhoGDIbeta lacking the N-terminal regulatory domain suppresses metastasis by promoting anoikis in v-src-transformed cells.
MedLine Citation:
PMID:  17111235     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rho guanine nucleotide dissociation inhibitors (RhoGDIs) regulate the activity of Rho family GTPases. RhoGDIbeta (LyGDI/GDID4/RhoGDI2) has two caspase cleavage sites after Asp19 and Asp55. The resulting cleavage products, DeltaN(1-19)RhoGDIbeta and DeltaN(1-55)RhoGDIbeta, are expressed in cells under conditions that activate caspases. DeltaN(1-19)RhoGDIbeta, which can inhibit GDP dissociation, is implicated in the process of apoptosis, whereas the physiological roles for DeltaN(1-55)RhoGDIbeta, which lacks the ability to inhibit GDP dissociation, are largely unknown. To explore the roles of DeltaN(1-55)RhoGDIbeta, we examined the phenotypes of v-src-transformed metastatic fibroblasts transfected with plasmids for expressing DeltaN(1-55)RhoGDIbeta. Although the expression of DeltaN(1-55)RhoGDIbeta had no effect on the rate of growth in vitro, it suppressed experimental metastasis and decreased the rate of growth in vivo. In addition, DeltaN(1-55)RhoGDIbeta-expressing cells had enhanced adhesion to fibronectin, laminin, and collagens but reduced retention in the lung after intravenous injection. Also, the expression of DeltaN(1-55)RhoGDIbeta promoted anoikis without affecting the levels of activated Rac1 or Cdc42. Furthermore, DeltaN(1-55)RhoGDIbeta did not affect the expression or phosphorylation of focal adhesion kinase, p44/p42 mitogen-activated protein kinases, or Akt1 before or after induction of anoikis. Thus, DeltaN(1-55)RhoGDIbeta appears to promote anoikis by undefined mechanisms, thereby suppressing metastasis in v-src-transformed fibroblasts.
Authors:
Takahide Ota; Masayo Maeda; Shiho Sakita-Suto; Xinwen Zhou; Manabu Murakami; Tsutomu Takegami; Masaaki Tatsuka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-17
Journal Detail:
Title:  Clinical & experimental metastasis     Volume:  23     ISSN:  0262-0898     ISO Abbreviation:  Clin. Exp. Metastasis     Publication Date:  2006  
Date Detail:
Created Date:  2007-01-31     Completed Date:  2007-03-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8409970     Medline TA:  Clin Exp Metastasis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  323-34     Citation Subset:  IM    
Affiliation:
Division of Molecular Oncology and Virology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. takahide@kanazawa-med.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoikis*
Cell Transformation, Neoplastic
Genes, src
Guanine Nucleotide Dissociation Inhibitors / chemistry,  physiology*
Male
Mice
Mice, Inbred BALB C
Neoplasm Metastasis / prevention & control*
Signal Transduction
Chemical
Reg. No./Substance:
0/Guanine Nucleotide Dissociation Inhibitors; 133312-85-3/rho guanine nucleotide dissociation inhibitors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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