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: UMLS:C0178874 (
tumor progression
)
40,807
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The tumor microenvironment (TME) and metabolic reprogramming have been implicated in cancer development and progression. However, the link between TME, metabolism, and
cancer progression
in lung cancer is unclear. In the present study, we identified
IMPAD1
from the conditioned medium of highly invasive CL1-5. High expression of
IMPAD1
was associated with a poorer clinical phenotype in lung cancer patients, with reduced survival and increased lymph node metastasis. Knockdown of
IMPAD1
significantly inhibited migration/invasion abilities and metastasis in vitro and in vivo. Upregulation of
IMPAD1
and subsequent accumulation of AMP in cells increased the pAMPK, leading to Notch1 and HEY1 upregulation. As AMP is an ADORA1 agonist, treatment with ADORA1 inhibitor reduced the expression of pAMPK and HEY1 expression in
IMPAD1
-overexpressing cells.
IMPAD1
caused mitochondria dysfunction by inhibiting mitochondrial Complex I activity, which reduced mitochondrial ROS levels and activated the AMPK-HEY1 pathway. Collectively this study supports the multipotent role of
IMPAD1
in promotion of lung cancer metastasis by simultaneously increasing AMP levels, inhibition of Complex I activity to decrease ROS levels, thereby activating AMPK-Notch1-HEY1 signaling, and providing an alternative metabolic pathway in energy stress conditions.
...
PMID:IMPAD1 functions as mitochondrial electron transport inhibitor that prevents ROS production and promotes lung cancer metastasis through the AMPK-Notch1-HEY1 pathway. 3241 95
