[en] INTRODUCTION: Colorectal cancer remains a public health issue and most colon cancer patients succumb to the development of metastases. Using a specific protocol of pressure-assisted interstitial fluid extrusion to recover soluble biomarkers, we identified paladin as a potential colon cancer liver metastases biomarker. METHODS: Using shRNA gene knockdown, we explored the biological function of paladin in colon cancer cells and investigated the phospho-proteome within colon cancer cells. We successively applied in vitro migration assays, in vivo metastasis models and co-immunoprecipitation experiments. RESULTS: We discovered that paladin is required for colon cancer cell migration and metastasis, and that paladin depletion altered the phospho-proteome within colon cancer cells. Data are available via ProteomeXchange with identifier PXD030803. Thanks to immunoprecipitation experiments, we demonstrated that paladin, was interacting with SSH1, a phosphatase involved in colon cancer metastasis. Finally, we showed that paladin depletion in cancer cells results in a less dynamic actin cytoskeleton. CONCLUSIONS: Paladin is an undervalued protein in oncology. This study highlights for the first time that, paladin is participating in actin cytoskeleton remodelling and is required for efficient cancer cell migration.
Research center :
GIGA-LRM - GIGA Cancer-Metastases Research Laboratory - ULiège
Peiffer, Raphaël ; Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Agirman, Ferman ; Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Maloujahmoum, Naïma ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Vertommen, Didier
Turtoi, Andrei
Bellahcene, Akeila ; Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Castronovo, Vincenzo ✱; Université de Liège - ULiège > GIGA > GIGA Cancer - Metastases Research Laboratory
Peulen, Olivier ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie dans le domaine des sciences médicales et biomédicales
✱ These authors have contributed equally to this work.
Language :
English
Title :
Paladin, overexpressed in colon cancer, is required for actin polymerisation and liver metastasis dissemination
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