RalB directly triggers invasion downstream Ras by mobilizing the Wave complex.
Elife
; 72018 10 15.
Article
in En
| MEDLINE
| ID: mdl-30320548
ABSTRACT
The two Ral GTPases, RalA and RalB, have crucial roles downstream Ras oncoproteins in human cancers; in particular, RalB is involved in invasion and metastasis. However, therapies targeting Ral signalling are not available yet. By a novel optogenetic approach, we found that light-controlled activation of Ral at plasma-membrane promotes the recruitment of the Wave Regulatory Complex (WRC) via its effector exocyst, with consequent induction of protrusions and invasion. We show that active Ras signals to RalB via two RalGEFs (Guanine nucleotide Exchange Factors), RGL1 and RGL2, to foster invasiveness; RalB contribution appears to be more important than that of MAPK and PI3K pathways. Moreover, on the clinical side, we uncovered a potential role of RalB in human breast cancers by determining that RalB expression at protein level increases in a manner consistent with progression toward metastasis. This work highlights the Ras-RGL1/2-RalB-exocyst-WRC axis as appealing target for novel anticancer strategies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ras Proteins
/
Ral GTP-Binding Proteins
/
Wiskott-Aldrich Syndrome Protein Family
Limits:
Female
/
Humans
Language:
En
Journal:
Elife
Year:
2018
Document type:
Article
Affiliation country:
Francia