Role of CSN5/JAB1 in Wnt/β-catenin activation in colorectal cancer cells.
CSN5/JAB1 is a critical subunit of the COP9 signalosome (CSN) and is overexpressed in many human cancers, but little is known about the role of CSN5 in colorectal cancer (CRC). To explore the functional role of CSN5 in colorectal tumorigenesis, we applied siRNA technology to silence CSN5 in HeLa, SW480, HCT116, HT29, and CaCo2 cells. CSN5 knock-down led to reduced β-catenin and phospho-bcatenin levels and this was paralleled by reduced CRC cell proliferation and reduced apoptosis rates, whereas the short-term β-catenin protein stability was enhanced by CSN5 knock-down in SW480 cells. Together, these data implicate the CSN in the pathogenesis of CRC via regulation of the Wnt/β-catenin pathway
Institute of Biochemistry & Molecular Cell Biology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany.
Anke K
AK
Schütz
Thomas
T
Hennes
Sandra
S
Jumpertz
Simone
S
Fuchs
Jürgen
J
Bernhagen
D017209:Apoptosis / Q000235:genetics; D000075686:COP9 Signalosome Complex; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex; D053148:Caspase 3