Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells.
EMBO Rep
; 19(6)2018 06.
Article
in En
| MEDLINE
| ID: mdl-29661856
ABSTRACT
The transcriptional regulators TAZ and YAP (TAZ/YAP) have emerged as pro-tumorigenic factors that drive many oncogenic traits, including induction of cell growth, resistance to cell death, and activation of processes that promote migration and invasion. Here, we report that TAZ/YAP reprogram cellular energetics to promote the dependence of breast cancer cell growth on exogenous glutamine. Rescue experiments with glutamine-derived metabolites suggest an essential role for glutamate and α-ketoglutarate (AKG) in TAZ/YAP-driven cell growth in the absence of glutamine. Analysis of enzymes that mediate the conversion of glutamate to AKG shows that TAZ/YAP induce glutamic-oxaloacetic transaminase (GOT1) and phosphoserine aminotransferase (PSAT1) expression and that TAZ/YAP activity positively correlates with transaminase expression in breast cancer patients. Notably, we find that the transaminase inhibitor aminooxyacetate (AOA) represses cell growth in a TAZ/YAP-dependent manner, identifying transamination as a potential vulnerable metabolic requirement for TAZ/YAP-driven breast cancer.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoproteins
/
Transcription Factors
/
Breast Neoplasms
/
Aspartate Aminotransferase, Cytoplasmic
/
Adaptor Proteins, Signal Transducing
/
Glutamine
/
Transaminases
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
EMBO Rep
Journal subject:
BIOLOGIA MOLECULAR
Year:
2018
Type:
Article
Affiliation country:
United States