ArticleCancer research2008
Prostate cancer induces bone metastasis through Wnt-induced bone morphogenetic protein-dependent and independent mechanisms.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 152 citations in OpenAlex.
- Spatial immune profiling of bone-metastatic castration-resistant prostate cancer reveals radium-223 immunomodulates the bone-tumor microenvironment.Prostate cancer and prostatic diseases · 2026Article
- Beyond resorption-driven coupling: a multi-layered framework for osteoclast-osteoblast communication and its therapeutic consequences.Frontiers in endocrinology · 2026Review
- Evolutionary conservation and cancer implications of the WNT signaling pathway.Medical oncology (Northwood, London, England) · 2025Review
- Recent advances in understanding the role of Wnt5a in prostate cancer and bone metastasis.Discover oncology · 2025Review
- Autophagy Associated Genes (ARGs) -Based Predictive Model AIDPS for Prostate Cancer.Journal of cellular and molecular medicine · 2025Article
- WNT5A is a putative epi-driver of prostate cancer metastasis to the bone.Cancer medicine · 2024Article
- Article
- BMP Stimulation Differentially Affects Phosphorylation and Protein Stability of β-Catenin in Breast Cancer Cell Lines.International journal of molecular sciences · 2024Article
- Article
- Review
- Retinoic Acid Receptor Activation Reduces Metastatic Prostate Cancer Bone Lesions by Blocking the Endothelial-to-Osteoblast Transition.Cancer research · 2022Article
- Fatty Acid Signaling Impacts Prostate Cancer Lineage Plasticity in an Autocrine and Paracrine Manner.Cancers · 2022Article
- Chromosome compartmentalization alterations in prostate cancer cell lines model disease progression.The Journal of cell biology · 2022Article
- Evolving cancer-niche interactions and therapeutic targets during bone metastasis.Nature reviews. Cancer · 2022Review
- Research progress of bone metastases: From disease recognition to clinical practice.Frontiers in oncology · 2022Review
- Wnt and β-Catenin Signaling in the Bone Metastasis of Prostate Cancer.Life (Basel, Switzerland) · 2021Review
- Osteoblasts Generate Testosterone From DHEA and Activate Androgen Signaling in Prostate Cancer Cells.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Effect of Dickkopf-1 (Dkk-1) and SP600125, a JNK Inhibitor, on Wnt Signaling in Canine Prostate Cancer Growth and Bone Metastases.Veterinary sciences · 2021Article
- Prognostic value of noggin protein expression in patients with resected gastric cancer.BMC cancer · 2021Article
- Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Prostate cancer (PCa) is frequently accompanied by osteosclerotic (i.e., excessive bone production) bone metastases. Although bone morphogenetic proteins (BMP) and Wnts are mediators of PCa-induced osteoblastic activity, the relation between them in PCa bone metastases is unknown. The goal of this study was to define this relationship. Wnt3a and Wnt5a administration or knockdown of DKK-1, a Wnt inhibitor, induced BMP-4 and 6 expression and promoter activation in PCa cells. DKK-1 blocked Wnt activation of the BMP promoters. Transfection of C4-2B cells with axin, an inhibitor of canonical Wnt signaling, blocked Wnt3a but not Wnt5a induction of the BMP promoters. In contrast, Jnk inhibitor I blocked Wnt5a but not Wnt3a induction of the BMP promoters. Wnt3a, Wnt5a, and conditioned medium (CM) from C4-2B or LuCaP23.1 cells induced osteoblast differentiation in vitro. The addition of DKK-1 and Noggin, a BMP inhibitor, to CM diminished PCa CM-induced osteoblast differentiation in a synergistic fashion. However, pretreatment of PCa cells with DKK-1 before collecting CM blocked osteoblast differentiation, whereas pretreatment with Noggin only partially reduced osteoblast differentiation, and pretreatment with both DKK-1 and Noggin had no greater effect than pretreatment with DKK-1 alone. Additionally, knockdown of BMP expression in C4-2B cells inhibited Wnt-induced osteoblastic activity. These results show that PCa promotes osteoblast differentiation through canonical and noncanonical Wnt signaling pathways that stimulate both BMP-dependent and BMP-independent osteoblast differentiation. These results show a clear link between Wnts and BMPs in PCa-induced osteoblast differentiation and provide novel targets, including the noncanonical Wnt pathway, for therapy of PCa.
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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.