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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7-8
pubmed:dateCreated
2007-1-31
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0262-0898
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
323-34
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
RhoGDIbeta lacking the N-terminal regulatory domain suppresses metastasis by promoting anoikis in v-src-transformed cells.
pubmed:affiliation
Division of Molecular Oncology and Virology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. takahide@kanazawa-med.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't