ArticleOncogene2025
PKA-driven SPP1 activation as a novel mechanism connecting the bone microenvironment to prostate cancer progression.
Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- The pseudouridine epitranscriptomic landscape of advanced prostate cancer therapeutic resistance identifies TIMM17A as a key player.Translational oncology · 2026Article
- Exosome-mediated miR-4660 delivery inhibits OPN promoted hepatoma cells aggression through targeting LGALS3BP.Journal of cell communication and signaling · 2026Article
- [Tumor-secreted dentin sialophosphoprotein induces oxaliplatin resistance in colorectal cancer through an integrin αvβ3-dependent pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Combined Dihydroartemisinin and Eupatilin Suppress Prostate Cancer through AR-Associated Ferroptosis and Modulation of Macrophage-Tumor Crosstalk.Research (Washington, D.C.) · 2026Article
- Relationship between SPP1 (Osteopontin) and extracellular matrix dynamics: a comprehensive review.Frontiers in medicine · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.