Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25796446
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Enzo E
; Santinon G
; Pocaterra A
; Aragona M
; Bresolin S
; Forcato M
; Grifoni D
; Pession A
; Zanconato F
; Guzzo G
; Bicciato S
; Dupont S
EMBO J
2015[May]; 34
(10
): 1349-70
PMID25796446
show ga
Increased glucose metabolism and reprogramming toward aerobic glycolysis are a
hallmark of cancer cells, meeting their metabolic needs for sustained cell
proliferation. Metabolic reprogramming is usually considered as a downstream
consequence of tumor development and oncogene activation; growing evidence
indicates, however, that metabolism on its turn can support oncogenic signaling
to foster tumor malignancy. Here, we explored how glucose metabolism regulates
gene transcription and found an unexpected link with YAP/TAZ, key transcription
factors regulating organ growth, tumor cell proliferation and aggressiveness.
When cells actively incorporate glucose and route it through glycolysis, YAP/TAZ
are fully active; when glucose metabolism is blocked, or glycolysis is reduced,
YAP/TAZ transcriptional activity is decreased. Accordingly, glycolysis is
required to sustain YAP/TAZ pro-tumorigenic functions, and YAP/TAZ are required
for the full deployment of glucose growth-promoting activity. Mechanistically we
found that phosphofructokinase (PFK1), the enzyme regulating the first committed
step of glycolysis, binds the YAP/TAZ transcriptional cofactors TEADs and
promotes their functional and biochemical cooperation with YAP/TAZ. Strikingly,
this regulation is conserved in Drosophila, where phosphofructokinase is required
for tissue overgrowth promoted by Yki, the fly homologue of YAP. Moreover, gene
expression regulated by glucose metabolism in breast cancer cells is strongly
associated in a large dataset of primary human mammary tumors with YAP/TAZ
activation and with the progression toward more advanced and malignant stages.
These findings suggest that aerobic glycolysis endows cancer cells with
particular metabolic properties and at the same time sustains transcription
factors with potent pro-tumorigenic activities such as YAP/TAZ.
|Acyltransferases
[MESH]
|Adaptor Proteins, Signal Transducing/metabolism
[MESH]
free
free
free
