BioSpace Collaborative

Academic/Biomedical Research
News & Jobs
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

NEWSLETTERS
Free Newsletters
Archive
My Subscriptions

NEWS
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE

CAREER NETWORK
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

HOTBEDS
Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Genetown
  Pharm Country
  BioCapital
  BioMidwest
  Bio NC
  BioForest
  Southern Pharm
  BioCanada East
  US Device
Europe
Asia

DIVERSITY

PROFILES
Company Profiles

INTELLIGENCE
Research Store

INDUSTRY EVENTS
Research Events
Post an Event
RESOURCES
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Biochemistry - Biotechnology - Chemistry - Molecular Biology - Oncology - Pharmacology - Physiology

Small Molecule-Based Promotion of PKCa-Mediated ß-Catenin Degradation Suppresses the Proliferation of CRT-Positive Cancer Cells
Published: Friday, October 05, 2012
Author: Jungsug Gwak et al.

by Jungsug Gwak, Jee-Hyun Lee, Young-Hwa Chung, Gyu-Yong Song, Sangtaek Oh

Aberrant accumulation of intracellular ß-catenin is a well recognized characteristic of several cancers, including prostate, colon, and liver cancers, and is a potential target for development of anticancer therapeutics. Here, we used cell-based small molecule screening to identify CGK062 as an inhibitor of Wnt/ß-catenin signaling. CGK062 promoted protein kinase Ca (PKCa)-mediated phosphorylation of ß-catenin at Ser33/Ser37, marking it for proteasomal degradation. This reduced intracellular ß-catenin levels and consequently antagonized ß-catenin response transcription (CRT). Pharmacological inhibition or depletion of PKCa abrogated CGK062-mediated phosphorylation and degradation of ß-catenin. In addition, CGK062 repressed the expression of the genes encoding cyclin D1, c-myc, and axin-2, ß-catenin target genes, and thus inhibited the growth of CRT-positive cancer cells. Furthermore, treatment of nude mice bearing PC3 xenograft tumors with CGK062 at doses of 50 mg/kg and 100 mg/kg (i.p.) significantly suppressed tumor growth. Our findings suggest that CGK062 exerts its anticancer activity by promoting PKCa-mediated ß-catenin phosphorylation/degradation. Therefore, CGK062 has significant therapeutic potential for the treatment of CRT-positive cancers.
  More...

 

//-->