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

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.

SUBMITTER: Rademaker G

PROVIDER: S-EPMC9325978 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Paladin, a pseudo-phosphatase overexpressed in colon cancer, is required for actin polymerization and liver metastasis dissemination

Project description:Colorectal cancer remains a public health issue and most of colon cancer patients succumb to the development of metastases. Using a specific protocol, we identified paladin as a potential colon cancer liver metastases biomarker. We then explored the biological function of paladin in colon cancer cells. We discovered that paladin is required for cell migration and metastasis. We reported that paladin depletion altered the phospho-proteome within colon cancer cells. Thanks to immuno-precipitation experiments, we demonstrated that paladin was interacting with SSH-1, a phosphatase involved in colon cancer metastasis. Finally, we showed that paladin depletion in cancer cells altered the interaction between SSH-1 and actin, which results in a less dynamic actin cytoskeleton. In conclusion, paladin is an under undervalued protein in oncology participating in actin cytoskeleton remodelling and necessary for an efficient cancer cell migration

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