title: Syntenin controls migration, growth, proliferation, and cell cycle progression in cancer cells.
abstract: The scaffold protein syntenin abounds during fetal life where it is important for developmental movements. In human adulthood, syntenin gain-of-function is increasingly associated with various cancers and poor prognosis. Depending on the cancer model analyzed, syntenin affects various signaling pathways. We previously have shown that syntenin allows syndecan heparan sulfate proteoglycans to escape degradation. This indicates that syntenin has the potential to support sustained signaling of a plethora of growth factors and adhesion molecules. Here, we aim to clarify the impact of syntenin loss-of-function on cancer cell migration, growth, and proliferation, using cells from various cancer types and syntenin shRNA and siRNA silencing approaches. We observed decreased migration, growth, and proliferation of the mouse melanoma cell line B16F10, the human colon cancer cell line HT29 and the human breast cancer cell line MCF7. We further documented that syntenin controls the presence of active β1 integrin at the cell membrane and G1/S cell cycle transition as well as the expression levels of CDK4, Cyclin D2, and Retinoblastoma proteins. These data confirm that syntenin supports the migration and growth of tumor cells, independently of their origin, and further highlight the attractiveness of syntenin as potential therapeutic target.
authors.affiliation: Laboratory for Signal Integration in Cell Fate Decision, Department of Human Genetics, KU Leuven Leuven, Belgium ; Centre de Recherche en Cancérologie de Marseille, Aix-Marseille Université Marseille, France ; Inserm U1068, Institut Paoli-Calmettes Marseille, France ; Centre National de la Recherche Scientifique, UMR7258 Marseille, France.
authors.forename: Rudra
authors.initials: R
authors.lastname: Kashyap
authors.affiliation: Laboratory for Signal Integration in Cell Fate Decision, Department of Human Genetics, KU Leuven Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Roucourt
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Aix-Marseille Université Marseille, France ; Inserm U1068, Institut Paoli-Calmettes Marseille, France ; Centre National de la Recherche Scientifique, UMR7258 Marseille, France.
authors.forename: Frederique
authors.initials: F
authors.lastname: Lembo
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Aix-Marseille Université Marseille, France ; Inserm U1068, Institut Paoli-Calmettes Marseille, France ; Centre National de la Recherche Scientifique, UMR7258 Marseille, France.
authors.forename: Joanna
authors.initials: J
authors.lastname: Fares
authors.affiliation: Laboratory for Signal Integration in Cell Fate Decision, Department of Human Genetics, KU Leuven Leuven, Belgium.
authors.forename: Ane Marcos
authors.initials: AM
authors.lastname: Carcavilla
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Aix-Marseille Université Marseille, France ; Inserm U1068, Institut Paoli-Calmettes Marseille, France ; Centre National de la Recherche Scientifique, UMR7258 Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Restouin
authors.affiliation: Laboratory for Signal Integration in Cell Fate Decision, Department of Human Genetics, KU Leuven Leuven, Belgium ; Centre de Recherche en Cancérologie de Marseille, Aix-Marseille Université Marseille, France ; Inserm U1068, Institut Paoli-Calmettes Marseille, France ; Centre National de la Recherche Scientifique, UMR7258 Marseille, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Zimmermann
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Aix-Marseille Université Marseille, France ; Inserm U1068, Institut Paoli-Calmettes Marseille, France ; Centre National de la Recherche Scientifique, UMR7258 Marseille, France.
authors.forename: Rania
authors.initials: R
authors.lastname: Ghossoub
keywords: PDZ proteins; cancer cell growth; cancer cell migration; cancer cell proliferation; cell cycle; syndecan; syntenin