Linked Life Data

21180766

Source:http://linkedlifedata.com/resource/pubmed/id/21180766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-2-15
pubmed:abstractText
RKIP-1 is a metastasis suppressor that is frequently downregulated in aggressive cancers. However, the consequences of RKIP loss in primary or immortalized cells have not yet been explored. Using HEK-293 RKIP depleted (termed HEK-499) and Flp-In T-Rex-293 RKIP inducible cell lines combined with whole transcriptome analysis, we show that RKIP-1 silencing accelerates DNA synthesis and G1/S transition entry by inducing the expression of cdc6, MCM 2, 4, 6, 7, cdc45L, cyclin D2, cyclin E2, cyclin D1, SKP2 and the downregulation of p21(cip1). Moreover, RKIP depletion accelerates the time from nuclear envelop breakdown (NEB) to anaphase markedly, while the upregulation of RKIP shortened the NEB to anaphase time. We show that RKIP depletion induces the expression of NEK6, a molecule known to enhance G2/M transition, and down-regulates G2/M checkpoint molecules like Aurora B, cyclin G1 and sertuin that slow the G2/M transition time. These subtle changes in the kinetics of the cell cycle culminate in a higher proliferation rate of HEK-499 compared to control cells. Finally, we show that RKIP depletion enhances cellular motility by inducing the expression/stabilization of ?-catenin, vimentin, MET and PAK1. Overall, our data suggest that modulation of the cell cycle checkpoints and motility by RKIP may be fundamental to its metastasis suppressive function in cancer and that RKIP role in a cell is more intricate and diverse than previously thought.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1742-2051
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
928-41
pubmed:dateRevised
2011-11-8
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
RAF kinase inhibitory protein (RKIP) modulates cell cycle kinetics and motility.
pubmed:affiliation
Department of Pathology, University of Kuwait, Faculty of Medicine, Health Sciences Center, 13110, Kuwait. fahd@al-mulla.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't