Paladin, overexpressed in colon cancer, is required for actin polymerisation and liver metastasis dissemination

Autor: Gilles Rademaker, Brunella Costanza, Sébastien Pyr dit Ruys, Raphaël Peiffer, Ferman Agirman, Naïma Maloujahmoum, Didier Vertommen, Andrei Turtoi, Akeila Bellahcène, Vincent Castronovo, Olivier Peulen
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Oncogenesis, Vol 11, Iss 1, Pp 1-10 (2022)
Druh dokumentu: article
ISSN: 2157-9024
DOI: 10.1038/s41389-022-00416-4
Popis: 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.
Databáze: Directory of Open Access Journals
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