FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer - Archive ouverte HAL Access content directly
Journal Articles Digestive and Liver Disease Year : 2022

FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer

(1) , (2) , (3, 4) , (2) , (5) , (6) , (7) , (8) , (9) , (10) , (11) , (12) , (13) , (14) , (15) , (1, 16) , (1) , (17, 18) , (19) , (16) , (19) , (20) , (21) , (22, 23) , (3) , (20) , (1)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Boris Guiu
  • Function : Author

Abstract

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.
Fichier principal
Vignette du fichier
Randrian et al - 2022 - FFCD 1709-SIRTCI phase II trial.pdf (235.99 Ko) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03906999 , version 1 (24-01-2023)

Identifiers

Cite

Violaine Randrian, Simon Pernot, Karine Le Malicot, Vittorio Catena, Isabelle Baumgaertner, et al.. FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer. Digestive and Liver Disease, 2022, 54 (7), pp.857-863. ⟨10.1016/j.dld.2022.04.024⟩. ⟨hal-03906999⟩
0 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More