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pmid:35882839

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

Gilles Rademaker · Brunella Costanza · Sébastien Pyr Dit Ruys · Raphaël Peiffer · Ferman Agirman · Naïma Maloujahmoum · Didier Vertommen · Andrei Turtoi · Akeila Bellahcène · Vincent Castronovo · Olivier Peulen

Oncogenesis · 2022 doi:10.1038/s41389-022-00416-4

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Paladin, overexpressed in colon cancer, is required for actin polymerisation and liver metastasis dissemination.
doi
10.1038/s41389-022-00416-4
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Gilles Rademaker
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Brunella Costanza
[2]
Sébastien Pyr Dit Ruys
[3]
Raphaël Peiffer
[4]
Ferman Agirman
[5]
Naïma Maloujahmoum
[6]
Didier Vertommen
[7]
Andrei Turtoi
[8]
Akeila Bellahcène
[9]
Vincent Castronovo
[10]
Olivier Peulen
journal
Oncogenesis
year
2022
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.
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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.\nMETHODS: 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.\nRESULTS: 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. 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