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

doi:10.1038/s41389-022-00416-4

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

Oncogenesis. 2022 Jul 26;11(1):42. doi: 10.1038/s41389-022-00416-4.

Authors

Affiliations

¹ Metastasis Research Laboratory, Giga Cancer University of Liège, Liège, Belgium.
² Department of Anatomy, University of California, San Francisco, San Francisco, CA, 94143, USA.
³ Department of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Milan, 20139, Italy.
⁴ MassProt platform, de Duve Institute, Université Catholique de Louvain (UCLouvain), Brussels, Belgium.
⁵ Tumor microenvironment and resistance to treatment Laboratory, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), Institut Régional du Cancer de Montpellier (ICM), Montpellier, France.
⁶ Metastasis Research Laboratory, Giga Cancer University of Liège, Liège, Belgium. [email protected].

^# Contributed equally.

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.