4.6 Article

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

Journal

ONCOGENESIS
Volume 11, Issue 1, Pages -

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SPRINGERNATURE
DOI: 10.1038/s41389-022-00416-4

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Paladin is identified as a potential biomarker for colon cancer liver metastases, and its depletion inhibits colon cancer cell migration and metastasis.
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.

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