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:4.2.1.22 (
cystathionine beta-synthase
)
965
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Elevated lipid metabolism is implicated in poor survival in ovarian cancer (OC) and other cancers; however, current lipogenesis-targeting strategies lack cancer cell specificity. Here, we identify a novel role of
cystathionine beta-synthase
(
CBS
), a sulphur amino acid metabolizing enzyme highly expressed in several ovarian cancer cell lines, in driving deregulated lipid metabolism in OC. We examined the role of
CBS
in regulation of triglycerides, cholesterol and lipogenic enzymes via the lipogenic transcription factors SREBP1 and SREBP2.
CBS
silencing attenuated the expression of number of key enzymes involved in lipid synthesis (FASN and
ACC1
). Additionally
CBS
abrogates lipid uptake in OC cells. Gene silencing of
CBS
or SREBPs abrogated cellular migration and invasion in OC, while ectopic expression of SREBPs can rescue phenotypic effects of
CBS
silencing by restoring cell migration and invasion. Mechanistically,
CBS
represses SREBP1 and SREBP2 at the transcription levels by modulating the transcription factor Sp1. We further established the roles of both
CBS
and SREBPs in regulating ovarian tumor growth in vivo. In orthotopic tumor models,
CBS
or SREBP silencing resulted in reduced tumor cells proliferation, blood vessels formation and lipid content. Hence, cancer-selective disruption of the lipid metabolism pathway is possible by targeting
CBS
and, at least for OC, promises a profound benefit.
...
PMID:Role of cystathionine beta synthase in lipid metabolism in ovarian cancer. 2645 59
