Journal article
Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer
Cancer cell, Vol.42(10), pp.1676-1692.e11
10/14/2024
DOI: 10.1016/j.ccell.2024.08.018
PMID: 39303726
Abstract
Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10 high PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances F10 expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies.
Details
- Title: Subtitle
- Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer
- Creators
- Bianca Cali - Università della Svizzera italianaMartina Troiani - Università della Svizzera italianaSilvia Bressan - Università della Svizzera italianaGiuseppe Attanasio - Università della Svizzera italianaSara Merler - Ente Ospedaliero CantonaleViola Moscarda - Università della Svizzera italianaSimone Mosole - Università della Svizzera italianaElena Ricci - Università della Svizzera italianaChristina Guo - Royal Marsden NHS Foundation TrustWei Yuan - Royal Marsden NHS Foundation TrustLewis Gallagher - Royal Marsden NHS Foundation TrustArian Lundberg - Royal Marsden NHS Foundation TrustIlona Bernett - Royal Marsden NHS Foundation TrustInes Figueiredo - Royal Marsden NHS Foundation TrustRydell Alvarez Arzola - Center of Molecular Immunology (Cuba)Ernesto Bermudez Abreut - Center of Molecular Immunology (Cuba)Mariantonietta D'Ambrosio - Istituto Oncologico RomagnoloNicolo Bancaro - Università della Svizzera italianaDaniela Brina - Università della Svizzera italianaSara Zumerle - University of PaduaEmiliano Pasquini - Università della Svizzera italianaMartino Maddalena - Università della Svizzera italianaPing Lai - Università della Svizzera italianaManuel Colucci - Università della Svizzera italianaNicolo Pernigoni - Università della Svizzera italianaAndrea Rinaldi - Università della Svizzera italianaDavide Minardi - University of PaduaAlessandro Morlacco - University of PaduaFabrizio Dal Moro - University of PaduaMarianna Sabbadin - University of PaduaFrancesca Galuppini - University of PaduaMatteo Fassan - University of PaduaJan Hendrik Ruschoff - University Hospital ZurichHolger Moch - University Hospital ZurichPasquale Rescigno - Candiolo Cancer InstituteEdoardo Francini - Ente Ospedaliero CantonaleCalogero Saieva - Prevention InstituteMikol Modesti - Ente Ospedaliero CantonaleJean-Philippe Theurillat - Istituto Oncologico RomagnoloSilke Gillessen - Ente Ospedaliero CantonalePetra Wilgenbus - Johannes Gutenberg University MainzClaudine Graf - Johannes Gutenberg University MainzWolfram Ruf - Johannes Gutenberg University MainzJohann de Bono - Royal Marsden NHS Foundation TrustAndrea Alimonti - Ente Ospedaliero Cantonale
- Resource Type
- Journal article
- Publication Details
- Cancer cell, Vol.42(10), pp.1676-1692.e11
- DOI
- 10.1016/j.ccell.2024.08.018
- PMID
- 39303726
- ISSN
- 1535-6108
- eISSN
- 1878-3686
- Publisher
- Elsevier
- Number of pages
- 29
- Grant note
- 201274 / SNSF Sinergia; Swiss National Science Foundation (SNSF) SNSF Excel-lence grant; Swiss National Science Foundation (SNSF) 21A009; ERC-CoG 683136 / Novartis Foundation; Novartis 318346496; SFB1292/2 TP10; PCF-19CHAL08 / ISREC Foundation, Fidinam Foundation
- Language
- English
- Date published
- 10/14/2024
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985221246102771
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