NEWS
SEPTEMBER 10 , 2008
RSK connects MAPK to mTORC1 via RAPTOR
Philippe Roux and his collaborators find molecular link between signaling pathways involved in cancer.
A team from the Institute for Research in Immunology and Cancer (IRIC) of the Université de Montréal has just published research elucidating a mechanism whereby cancer cells hijack intracellular signaling pathways to escape cell proliferation controls. The discovery, which is reported in the September 9 issue of Current Biology, opens up new therapeutic avenues to block tumor growth.
| “The image that comes to my mind when I think of intracellular signaling is that of rows of dominos that start to fall on each other the moment a first piece has fallen, explains Philippe Roux, director of the Laboratory of Cell Signaling and Proteomics at IRIC and corresponding author of the paper. Sometimes the fall of a single piece can set in motion two rows of dominos, each of which follows its own distinct path. We have now identified one of those key pieces, a protein which acts in parallel on two signaling pathways involved in cancer and which might therefore constitute an excellent therapeutic target.” |
Philippe Roux, principal investigator, and Audrey Carrière, postdoctoral fellow |
The work of Philippe Roux and his collaborators arose from an unexpected result: treatment of cells with factors that activate the MAPK signaling pathway also leads to activation of the mTOR pathway. Crosstalk between these two signaling pathways, which were thought to run their own separate way, actually makes sense. It allows cells to integrate signals that trigger proliferation (MAPK pathway) and those that convey information about energetic status and nutrient availability (mTOR pathway). The IRIC research team has now succeeded in identifying the molecular players at the junction of the two pathways. They are the RSK proteins, key components of the MAPK pathways which, as was shown by the IRIC team, also act at the level of the Raptor protein in the mTOR pathway. By using RNA interference (RNAi) to block the synthesis of RSK proteins, IRIC scientists were able to show that Raptor is no longer activated by proliferative signals in the absence of RSK. Furthermore, using sophisticated proteomics tools they identified the sites of Raptor targeted by the RSK proteins. This proteomic analysis, which is essential to decipher the precise mechanism of activation of Raptor, was made possible through a close collaboration with Pierre Thibault, director of the Proteomics and Bioanalytical Mass Spectrometry Laboratory at IRIC and professor in the department of chemistry at UdeM.
Philippe Roux set up the Laboratory of Cell Signaling and Proteomics at IRIC in 2006 after postdoctoral training in the laboratory of John Blenis at Harvard Medical School. In less than two years, the young researcher, who is also assistant professor in the department of pathology and cell biology, recruited a team of 7 people and secured funds from national and international funding agencies. In particular, he obtained a prestigious Career Development Award from the Human Frontier Science Program, an organization of 36 countries based in Strasbourg. Philippe Roux now intends to continue making his mark as an independent investigator in the field of cell signaling, a research area that has given rise to some of the targeted therapies that are now revolutionizing the treatment of cancer and that is incidentally quite fond of acronyms.
The paper published today in Current Biology is entitled “Oncogenic MAPK Signaling Stimulates mTORC1 Activity by Promoting RSK-mediated Raptor Phosphorylation”. In addition to Pierre Thibault and Philippe Roux, the authors are Audrey Carrière, postdoctoral fellow and first author, Marie Cargnello and Louis-André Julien, graduate students, Huanhuan Gao, research assistant and Éric Bonneil, manager of the proteomics platform at IRIC. The paper is available online at doi:10.1016/j.cub.2008.07.078.
Information
Carolyne Lord
Media Relations Officer
IRIC | Université de Montréal
514.343.7282
carolyne.lord@umontreal.ca
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