Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.1.177 (
BIS
)
957
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glioblastoma stem cells (GSCs) are a subpopulation of highly tumorigenic and stem-like cells that are responsible for resistance to conventional therapy. Bcl-2-intreacting cell death suppressor (
BIS
; also known as BAG3) is an anti-apoptotic protein that is highly expressed in human cancers with various origins, including glioblastoma. In the present study, to investigate the role of
BIS
in GSC subpopulation, we examined the expression profile of
BIS
in A172 and U87-MG glioblastoma cell lines under specific in vitro culture conditions that enrich GSC-like cells in spheres. Both
BIS
mRNA and protein levels significantly increased under the sphere-forming condition as compared with standard culture conditions.
BIS
depletion resulted in notable decreases in sphere-forming activity and was accompanied with decreases in SOX-2 expression. The expression of STAT3, a master regulator of stemness, also decreased following
BIS
depletion concomitant with decreases in the nuclear levels of active phosphorylated STAT3, while ectopic STAT3 overexpression resulted in recovery of sphere-forming activity in
BIS
-knockdown glioblastoma cells. Additionally, immunoprecipitation and confocal microscopy revealed that
BIS
physically interacts with STAT3. Furthermore,
BIS
depletion increased STAT3 ubiquitination, suggesting that
BIS
is necessary for STAT3 stabilization in GSC-like cells.
BIS
depletion also affected epithelial-to-mesenchymal transition-related genes as evidenced by decrease in SNAIL and
MMP-2
expression and increase in E-cadherin expression in GSC-like cells. Our findings suggest that high levels of
BIS
expression might confer stem-cell-like properties on cancer cells through STAT3 stabilization, indicating that
BIS
is a potential target in cancer therapy.
...
PMID:BIS-mediated STAT3 stabilization regulates glioblastoma stem cell-like phenotypes. 2714 67
