dc.contributor
Institut Català de la Salut
dc.contributor
[Sanchis P, Sabater A] Department of Genitourinary Medical Oncology and The David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Laboratorio de Inflamación y Cáncer, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. CONICET-Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina. Universidad Argentina de la Empresa (UADE), Instituto de Tecnología (INTEC), Buenos Aires, Argentina. [Lechuga J, Rada J, Seniuk R, Pascual G] Laboratorio de Inflamación y Cáncer, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. CONICET-Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina. [Mateo J] Prostate Cancer Research Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Anselmino N] Department of Genitourinary Medical Oncology and The David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Prostate Cancer Research Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Sanchis, Pablo Antonio
dc.contributor.author
Sabater, Agustina
dc.contributor.author
Lechuga, Julia
dc.contributor.author
Rada, Jimena
dc.contributor.author
Seniuk, Rocio
dc.contributor.author
Pascual, Gaston Mario
dc.contributor.author
Anselmino, Nicolas
dc.contributor.author
Mateo, Joaquin
dc.date.issued
2025-10-14T10:20:43Z
dc.date.issued
2025-10-14T10:20:43Z
dc.date.issued
2025-10-07
dc.identifier
Sanchis P, Sabater A, Lechuga J, Rada J, Seniuk R, Pascual G, et al. PKA-driven SPP1 activation as a novel mechanism connecting the bone microenvironment to prostate cancer progression. Oncogene. 2025 Oct 7;44:3568-79.
dc.identifier
http://hdl.handle.net/11351/13853
dc.identifier
10.1038/s41388-025-03511-z
dc.identifier
001541860800001
dc.description.abstract
Bone microenvironment; Progression; Prostate cancer
dc.description.abstract
Microambiente óseo; Progresión; Cáncer de próstata
dc.description.abstract
Microambient ossi; Progressió; Càncer de pròstata
dc.description.abstract
Prostate cancer (PCa) bone metastasis (BM) poses a significant clinical challenge due to the heterogeneity of treatment responses and patient outcomes. In this study, we examined the role of Protein Kinase A (PKA) signaling in modulating the expression of osteopontin (SPP1/OPN), a protein associated with poor prognosis, within a subset of PCa BM patients. By integrating multi-omics results we identified a novel mechanism in which bone-derived type-I collagen (Col1a1) and fibronectin (Fn1) stimulate SPP1 expression in PCa cells through the activation of PKA signaling. This bone-induced regulation of SPP1 was confirmed both in vitro, using PCa-bone co-culture systems (PC3 or C42B/MC3T3 cell lines), and in vivo, using cell lines' engraftments and patient-derived xenografts (PDX) grown intrafemorally. Importantly, clinical data from longitudinal patient samples revealed that treatment with enzalutamide, an androgen receptor (AR) inhibitor, led to an increase in PKA signaling and corresponding SPP1 expression in a subpopulation of patients, highlighting the relevance of the PKA/SPP1 axis in disease progression under AR-targeted therapies. Overall, we underscored the critical role of the bone microenvironment in influencing PCa progression, pointing out to SPP1/OPN as a biomarker for identifying tumors with active PKA signaling, which could serve to manage resistance to AR-directed treatments.
dc.format
application/pdf
dc.publisher
Springer Nature
dc.relation
https://doi.org/10.1038/s41388-025-03511-z
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Ossos - Càncer - Tractament
dc.subject
Pròstata - Càncer - Tractament
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DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms
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Other subheadings::Other subheadings::Other subheadings::/drug therapy
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PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment
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DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression
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DISEASES::Neoplasms::Neoplasms by Site::Bone Neoplasms
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ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata
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Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
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FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral
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ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::progresión de la enfermedad
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias óseas
dc.title
PKA-driven SPP1 activation as a novel mechanism connecting the bone microenvironment to prostate cancer progression
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
