Phosphoethanolamine Accumulation Protects Cancer Cells under Glutamine Starvation through Downregulation of PCYT2.
Cell Rep
; 29(1): 89-103.e7, 2019 10 01.
Article
in En
| MEDLINE
| ID: mdl-31577958
ABSTRACT
Tolerance to severe tumor microenvironments, including hypoxia and nutrient starvation, is a common feature of aggressive cancer cells and can be targeted. However, metabolic alterations that support cancer cells upon nutrient starvation are not well understood. Here, by comprehensive metabolome analyses, we show that glutamine deprivation leads to phosphoethanolamine (PEtn) accumulation in cancer cells via the downregulation of PEtn cytidylyltransferase (PCYT2), a rate-limiting enzyme of phosphatidylethanolamine biosynthesis. PEtn accumulation correlated with tumor growth under nutrient starvation. PCYT2 suppression was partially mediated by downregulation of the transcription factor ELF3. Furthermore, PCYT2 overexpression reduced PEtn levels and tumor growth. In addition, PEtn accumulation and PCYT2 downregulation in human breast tumors correlated with poor prognosis. Thus, we show that glutamine deprivation leads to tumor progression by regulating PE biosynthesis via the ELF3-PCYT2 axis. Furthermore, manipulating glutamine-responsive genes could be a therapeutic approach to limit cancer progression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA Nucleotidyltransferases
/
Starvation
/
Down-Regulation
/
Ethanolamines
/
Glutamine
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2019
Document type:
Article