View Entire Collection
By Clinical Topic
By State Requirement
Diabetes – Summer 2012
Future of Nursing Initiative
Heart Failure - Fall 2011
Influenza - Winter 2011
Nursing Ethics - Fall 2011
Trauma - Fall 2010
Traumatic Brain Injury - Fall 2010
Fluids & Electrolytes
FRIDAY, Sept. 16 (HealthDay News) -- Liver X receptor (LXR) agonists cause inducible degrader of low-density lipoprotein receptor (LDLR)(IDOL)-mediated LDLR degradation and elevated expression of the ABCA1 cholesterol efflux transporter, which promotes cell death in a glioblastoma model, according to an experimental study published online Sept. 15 in Cancer Discovery.
Deliang Guo, Ph.D., from the Ohio State University Medical School in Columbus, and colleagues explored the role of cholesterol metabolism in glioblastoma pathogenesis, its association with epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K) signaling, and its possible therapeutic application. Studies were conducted on glioblastoma cell lines, xenograft models, and clinical samples, including those from patients treated with lapatinib, an EGFR tyrosine kinase inhibitor.
The investigators identified an EGFR mutation (EGFRvIII)-activated, PI3K/sterol regulatory element-binding protein 1 (SREBP-1)-dependent tumor survival pathway through the LDLR. The LXR agonist GW3965 targeted LDLR, resulting in IDOL-mediated LDLR degradation and raised expression of the ABCA1 cholesterol efflux transporter. These mechanisms promoted tumor cell death in an in vivo glioblastoma model.
"This study reveals that glioblastoma cells have devised a mechanism to subvert the normal pathways for feedback inhibition of cholesterol homeostasis via EGFRvIII and PI3K-dependent activation of SREBP-1," the authors write.
One of the study authors disclosed financial ties to the pharmaceutical and biopharmaceutical industries.
Full Text (subscription or payment may be required)
Sign up for our free enewsletters to stay up-to-date in your area of practice - or take a look at an archive of prior issues
Join our CESaver program to earn up to 100 contact hours for only $34.95
Explore a world of online resources
Back to Top