A negative feedback signaling network underlies oncogene-induced senescence.
Cancer Cell
; 10(6): 459-72, 2006 Dec.
Article
in En
| MEDLINE
| ID: mdl-17157787
ABSTRACT
Oncogene-induced senescence functions to limit tumor development. However, a complete understanding of the signals that trigger this type of senescence is currently lacking. We found that mutations affecting NF1, Raf, and Ras induce a global negative feedback response that potently suppresses Ras and/or its effectors. Moreover, these signals promote senescence by inhibiting the Ras/PI3K pathway, which can impact the senescence machinery through HDM2 and FOXO. This negative feedback program is regulated in part by RasGEFs, Sprouty proteins, RasGAPs, and MKPs. Moreover, these signals function in vivo in benign human tumors. Thus, the ultimate response to the aberrant activation of the Ras pathway is a multifaceted negative feedback signaling network that terminates the oncogenic signal and participates in the senescence response.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Genes, ras
/
Cellular Senescence
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer Cell
Journal subject:
NEOPLASIAS
Year:
2006
Document type:
Article
Affiliation country:
United States