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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
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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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. Finally, we showed that paladin depletion in cancer cells results in a less dynamic actin cytoskeleton.\nCONCLUSIONS: 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.", "claims": [{"id": "claim-method", "statement": "Kaplan–Meier curve was established and log-rank probability calculated.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35882839", "locator": "sections[3] \"Paladin is overexpressed in colon tumours and correlates with poor survival\" paragraph 2", "quote": "Kaplan–Meier curve was established and log-rank probability calculated."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (http://www.proteomexchange.org/) partner repository with the dataset identifier PXD030803 and 10.6019/PXD030803.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35882839", "locator": "sections[32] \"notes\" paragraph 1", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (http://www.proteomexchange.org/) partner repository with the dataset identifier PXD030803 and 10.6019/PXD030803."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We showed that, disease-free survival was significantly lower in patients with high paladin expression (p = 0.0277; Fig. 1E).", "kind": "quantitative", "target": {"value": 0.0277, "unit": "p-value", "tolerance": null, "source": "We showed that, disease-free survival was significantly lower in patients with high paladin expression (p = 0.0277; Fig. 1E)."}, "evidence": [{"asset": "source:pmid:35882839", "locator": "sections[3] \"Paladin is overexpressed in colon tumours and correlates with poor survival\" paragraph 2", "quote": "We showed that, disease-free survival was significantly lower in patients with high paladin expression (p = 0.0277; Fig. 1E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "We showed that, disease-free survival was significantly lower in patients with high paladin expression (p = 0.0277; Fig. 1E).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35882839"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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