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Article Dans Une Revue Oncogene Année : 2022

A proof of concept for targeting the PrPC - Amyloid β peptide interaction in basal prostate cancer and mesenchymal colon cancer

Résumé

Abstract The cellular prion protein PrP C partners with caveolin-1 (CAV1) in neurodegenerative diseases but whether this interplay occurs in cancer has never been investigated. By leveraging patient and cell line datasets, we uncover a molecular link between PrP C and CAV1 across cancer. Using cell-based assays, we show that PrP C regulates the expression of and interacts with CAV1. PrP C additionally controls the expression of the amyloid precursor protein APP and of the Aβ generating enzyme BACE1, and regulates the levels of Aβ, whose accumulation is a central event in Alzheimer’s disease. We further identify DKK1 and DKK3, involved in both Alzheimer’s disease and cancer progression, as targets of the PrP C -dependent axis. Finally, we establish that antibody-mediated blocking of the Aβ-PrP C interaction delays the growth of prostate cancer cell line-derived xenografts and prevents the development of metastases. Our data additionally support an enrichment of the Aβ-PrP C -dependent pathway in the basal subtype of prostate cancer, associated with anti-hormonal therapy resistance, and in mesenchymal colon cancer, associated with poor prognosis. Thus, based on a parallel with neurodegenerative diseases, our results bring to light an Aβ-PrP C axis and support the potential of targeting this pathway in patients with selected subtypes of prostate and colon cancer.

Dates et versions

hal-03752600 , version 1 (17-08-2022)

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Sophie Mouillet-Richard, Séverine Martin-Lannerée, Delphine Le Corre, Théo Hirsch, Alexandre Ghazi, et al.. A proof of concept for targeting the PrPC - Amyloid β peptide interaction in basal prostate cancer and mesenchymal colon cancer. Oncogene, 2022, ⟨10.1038/s41388-022-02430-7⟩. ⟨hal-03752600⟩
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