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- Title
Paladin, overexpressed in colon cancer, is required for actin polymerisation and liver metastasis dissemination.
- Authors
Rademaker, Gilles; Costanza, Brunella; Pyr dit Ruys, Sébastien; Peiffer, Raphaël; Agirman, Ferman; Maloujahmoum, Naïma; Vertommen, Didier; Turtoi, Andrei; Bellahcène, Akeila; Castronovo, Vincent; Peulen, Olivier
- Abstract
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.
- Publication
Oncogenesis, 2022, Vol 11, Issue 1, p1
- ISSN
2157-9024
- Publication type
Article
- DOI
10.1038/s41389-022-00416-4