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:1.6.5.2 (
NQO1
)
6,196
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Overexpression of
NQO1
is associated with poor prognosis in human cancers including lung, stomach, colon, cervical, and pancreatic cancers. However, the molecular mechanisms underlying the protumorigenic capacities of
NQO1
have not been fully elucidated. Here, we investigated this question and determined the molecular mechanisms underlying the roles of
NQO1
in glycolysis reprogramming, proliferation, and metastasis breast cancer (BC) cells. The results indicated that
NQO1
overexpression in BC cells raises glucose metabolism and metastasis related behaviors. Mechanistically,
NQO1
bound to
PKLR
, activated the AMPK and AKT/mTOR signaling pathway and consequently induced glycolytic reprogramming. In addition, 2-deoxy-d-glucose (2-DG) or 3-bromopyruvate (3-BrPA) influenced proliferation and regulated the expression of genes involved in the epithelial-to-mesenchymal transition (EMT) by restraining glycolytic reprogramming. Finally, overexpression of
NQO1
and
PKLR
in human BC tissues was remarkably related to lymph node (LN) metastasis and poor prognosis. Together, these results demonstrate that the
NQO1
/
PKLR
axis can promote the progression of BC by modulating glycolytic reprogramming and suggest that targeting
NQO1
and its downstream effectors are promising therapeutic targets for preventing the BC progression.
...
PMID:The NQO1/PKLR axis promotes lymph node metastasis and breast cancer progression by modulating glycolytic reprogramming. 3095 48
