RalB directly triggers invasion downstream Ras by mobilizing the Wave complex
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 activati...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/40474 |
| _version_ | 1811200746712989696 |
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| author | Giulia Zago Irina Veith Manish Kumar Singh Laetitia Fuhrmann Simon De Beco Amanda Remorino Saori Takaoka Marjorie Palmeri Frédérique Berger Nathalie Brandon Ahmed El Marjou Anne Vincent-Salomon Jacques Camonis Mathieu Coppey Maria Carla Parrini |
| author_facet | Giulia Zago Irina Veith Manish Kumar Singh Laetitia Fuhrmann Simon De Beco Amanda Remorino Saori Takaoka Marjorie Palmeri Frédérique Berger Nathalie Brandon Ahmed El Marjou Anne Vincent-Salomon Jacques Camonis Mathieu Coppey Maria Carla Parrini |
| author_sort | Giulia Zago |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:08:53Z |
| format | Article |
| id | doaj.art-54917d5394b24339880d13efb633fc1c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:08:53Z |
| publishDate | 2018-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-54917d5394b24339880d13efb633fc1c2022-12-22T03:52:27ZengeLife Sciences Publications LtdeLife2050-084X2018-10-01710.7554/eLife.40474RalB directly triggers invasion downstream Ras by mobilizing the Wave complexGiulia Zago0https://orcid.org/0000-0001-8280-1589Irina Veith1Manish Kumar Singh2Laetitia Fuhrmann3Simon De Beco4Amanda Remorino5Saori Takaoka6Marjorie Palmeri7Frédérique Berger8Nathalie Brandon9Ahmed El Marjou10Anne Vincent-Salomon11Jacques Camonis12Mathieu Coppey13Maria Carla Parrini14https://orcid.org/0000-0002-7082-9792Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; Department of Pathology, Institut Curie, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; LOCCO Group, UMR168, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; LOCCO Group, UMR168, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; Department of Biostatistics, Institut Curie, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; Protein Expression and Purification Core Facility, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; Department of Pathology, Institut Curie, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; LOCCO Group, UMR168, Paris, FranceInstitut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France; ART Group, Inserm U830, Paris, FranceThe 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.https://elifesciences.org/articles/40474InvasionRalbreast cancerExocystWaveoptogenetics |
| spellingShingle | Giulia Zago Irina Veith Manish Kumar Singh Laetitia Fuhrmann Simon De Beco Amanda Remorino Saori Takaoka Marjorie Palmeri Frédérique Berger Nathalie Brandon Ahmed El Marjou Anne Vincent-Salomon Jacques Camonis Mathieu Coppey Maria Carla Parrini RalB directly triggers invasion downstream Ras by mobilizing the Wave complex eLife Invasion Ral breast cancer Exocyst Wave optogenetics |
| title | RalB directly triggers invasion downstream Ras by mobilizing the Wave complex |
| title_full | RalB directly triggers invasion downstream Ras by mobilizing the Wave complex |
| title_fullStr | RalB directly triggers invasion downstream Ras by mobilizing the Wave complex |
| title_full_unstemmed | RalB directly triggers invasion downstream Ras by mobilizing the Wave complex |
| title_short | RalB directly triggers invasion downstream Ras by mobilizing the Wave complex |
| title_sort | ralb directly triggers invasion downstream ras by mobilizing the wave complex |
| topic | Invasion Ral breast cancer Exocyst Wave optogenetics |
| url | https://elifesciences.org/articles/40474 |
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