Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, France
Irina Veith
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, France
Manish Kumar Singh
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, France
Laetitia Fuhrmann
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; Department of Pathology, Institut Curie, Paris, France
Simon De Beco
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; LOCCO Group, UMR168, Paris, France
Amanda Remorino
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; LOCCO Group, UMR168, Paris, France
Saori Takaoka
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, France
Marjorie Palmeri
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, France
Frédérique Berger
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; Department of Biostatistics, Institut Curie, Paris, France
Nathalie Brandon
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, France
Ahmed El Marjou
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; Protein Expression and Purification Core Facility, Paris, France
Anne Vincent-Salomon
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; Department of Pathology, Institut Curie, Paris, France
Jacques Camonis
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, France
Mathieu Coppey
Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; LOCCO Group, UMR168, Paris, France
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.
