2026-04-17T02:46:49Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/135102025-09-30T02:08:40Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Martin-Martin, Natalia author Garcia-Longarte, Saioa author Lazcano, Uxue author Astobiza, Ianire author Bozal Basterra, Laura author Herranz Martín, Nicolás author Salca, Andrei author Corres-Mendizabal, Jon author Mateo, Joaquin author 2025-08-11T06:29:20Z 2025-08-11T06:29:20Z 2025-06-03 Cancer cell reprogramming; Prostate cancer; Single-cell transcriptomics Reprogramación de células cancerosas; Cáncer de próstata; Transcriptómica de células individuales Reprogramació de cèl·lules canceroses; Càncer de pròstata; Transcriptòmica de cèl·lules individuals Background: Metastatic hormone-naïve prostate cancer (mHNPC) is an infrequent form of this tumor type that is characterized by metastasis at the time of diagnosis and accounts for up to 50% of prostate cancer-related deaths. Despite the extensive characterization of localized and metastatic castration-resistant prostate cancer, the molecular characteristics of mHNPC remain largely unexplored. Results: Here, we provide the first extensive transcriptomics characterization of primary tumor specimens from patients with mHNPC. We generate discovery and validation bulk and single-cell RNA-seq datasets and perform integrative computational analysis in combination with experimental studies. Our results provide unprecedented evidence of the distinctive transcriptional profile of mHNPC and identify stroma remodeling as a predominant feature of these tumors. Importantly, we discover a central role for the SRY-box transcription factor 11 (SOX11) in triggering a heterotypic communication that is associated with the acquisition of metastatic properties. Conclusions: Our study will constitute an invaluable resource for a profound understanding of mHNPC that can influence patient management. This study was predominantly funded by the Spanish Association Against Cancer (AECC, GCTRA18006CARR to Carracedo, Gomis, Unda, Graupera and González-Billalabeitia as PIs) and AstraZeneca Jóvenes Investigadores 2023 Award (To Carracedo, Mateo, Mendizabal and Herranz). The work of A. Carracedo is supported by the Basque Department of Industry, Tourism, and Trade (Elkartek), the BBVA foundation (Becas Leonardo), the MICINN (PID2022-141553OB-I0 (FEDER/EU), Fundación Cris Contra el Cáncer (PR_EX_2021-22), Severo Ochoa Excellence Accreditation (CEX2021-001136-S), European Training Networks Project (H2020-MSCA-ITN-2020 955534), the Fundación Jesús Serra, iDIFFER network of Excellence (RED2022-134792-T), and the European Research Council (Consolidator Grant 819242). CIBERONC was co-funded with FEDER funds and funded by ISCIII. I. Mendizabal is supported by CRIS Contra El Cancer Foundation (PR_TPD_2020-19) and a Ramón y Cajal contract (RYC2023-044682-I) funded by the MCIN. U. Lazcano is supported by the AECC Foundation (PRDVZ245829LAZC). L. Bozal was supported by the AECC Foundation (POSTD19048BOZA). H. van Splunder received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 955951. M. Graupera is supported by Worldwide Cancer Research (WCR 21–0159). R. Gomis and M.T. Blasco were supported by the BBVA Foundation, Fundación Científica AECC (PRYGN223207GOMI), and MICINN (PID2022-143093OB-I00; FEDER/EU). J. Mateo is supported by CRIS Talent Award (TALENT20-10) and a Department of Defense CDMPR Physician-Science Award (PC220307). VHIO authors would like to acknowledge the Spanish State Agency for Research (Agencia Estatal de Investigación) for the financial support as a Center of Excellence Severo Ochoa (CEX2020-001024-S/AEI/https://doi.org/10.13039/501100011033), the Cellex Foundation for providing research facilities and equipment, FERO Foundation, and the CERCA Programme from Generalitat de Catalunya for their support. http://hdl.handle.net/11351/13510 Metàstasi Biòpsia Pròstata - Càncer - Aspectes genètics Factors de transcripció ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cytodiagnosis::Biopsy CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::SOX Transcription Factors::SOXC Transcription Factors DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms Other subheadings::Other subheadings::Other subheadings::/genetics DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis PHENOMENA AND PROCESSES::Chemical Phenomena::Biochemical Phenomena::Transcription, Genetic::Transcriptome TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::técnicas citológicas::citodiagnóstico::biopsia COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de unión al ADN::factores de transcripción SOX::factores de transcripción SOXC ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata Otros calificadores::Otros calificadores::Otros calificadores::/genética ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica FENÓMENOS Y PROCESOS::fenómenos químicos::fenómenos bioquímicos::transcripción genética::transcriptoma Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination