Linked Life Data

17018591

Source:http://linkedlifedata.com/resource/pubmed/id/17018591

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2006-10-4
pubmed:abstractText
Over 70% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced stage III and IV disease. In spite of aggressive therapy, locoregional disease recurs in 60% and metastatic disease develops in 15% to 25% of patients causing a major decline in quality and length of life. Therefore, there is a need to identify and understand genes that are responsible for inducing an aggressive HNSCC phenotype. Evidence has shown that protein kinase C (PKC) epsilon is a transforming oncogene and may play a role in HNSCC progression. In this study, we determine the downstream signaling pathway mediated by PKC epsilon to promote an aggressive HNSCC phenotype. RNA interference knockdown of PKC epsilon in UMSCC11A and UMSCC36, two highly invasive and motile HNSCC cell lines with elevated endogenous PKC epsilon levels, resulted in cells that were significantly less invasive and motile than the small interfering RNA-scrambled control transfectants; 51 +/- 5% (P < 0.006) and 49 +/- 3% (P < 0.010) inhibition in invasion and 69 +/- 1% (P < 0.0005) and 66 +/- 3% (P < 0.0001) inhibition in motility, respectively. PKC epsilon-deficient UMSCC11A clones had reduced levels of active and serine-phosphorylated RhoA and RhoC. Moreover, constitutive active RhoA completely rescued the invasion and motility defect, whereas constitutive active RhoC completely rescued the invasion and partially rescued the motility defect of PKC epsilon-deficient UMSCC11A clones. These results indicate that RhoA and RhoC are downstream of PKC epsilon and critical for PKC epsilon-mediated cell invasion and motility. Our study shows, for the first time, that PKC epsilon is involved in a coordinated regulation of RhoA and RhoC activation, possibly through direct post-translational phosphorylation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9379-84
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Targeted disruption of protein kinase C epsilon reduces cell invasion and motility through inactivation of RhoA and RhoC GTPases in head and neck squamous cell carcinoma.
pubmed:affiliation
Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI 48109, USA. qpan@med.umich.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural