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:3.2.1.23 (
beta-galactosidase
)
14,648
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Head and neck cancer (
HNSCC
) are one of the most common solid malignancies of the world, being responsible for over 350,000 deaths every year. Much of the complications in managing and treating
HNSCC
advent from the complex genetic and epigenetic landscape of the disease. Emerging information has shown promising results in targeting BRD4, an epigenetic regulator bromodomain that functions as a scaffold for transcription factors at promoters and super-enhancers. Here we show that by disrupting the interaction between BRD4 and histones using the bromodomain inhibitor JQ1,
HNSCC
cells undergo cell growth arrest followed by cellular senescence. Mechanistically, JQ1 negatively impacted the phosphorylation levels of SIRT1 along with the acetylation levels of mutant p53 (active). In vivo administration of JQ1 resulted in disruption of
HNSCC
growth along with the activation of cellular senescence, observed by the accumulation of DNA double-strand breaks, p16
ink4
, accumulation of senescence-associated
beta-galactosidase
, and loss of phosphorylated Sirt1
ser47
. Furthermore, we also demonstrate that JQ1 was efficient in reducing the population of cancer stem cells from
HNSCC
xenografts.
...
PMID:Interference with the bromodomain epigenome readers drives p21 expression and tumor senescence. 3126 75
