ArticleEndocrine-related cancer2014
RANK- and c-Met-mediated signal network promotes prostate cancer metastatic colonization.
Article in Endocrine-related cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 80 citations in OpenAlex.
- Pharmacodynamic study of radium-223 in men with bone metastatic castration resistant prostate cancer.PloS one · 2019Trial
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- Epigenetic regulation of breast cancer metastasis.Cancer metastasis reviews · 2024Review
- Androgen deprivation induces double-null prostate cancer via aberrant nuclear export and ribosomal biogenesis through HGF and Wnt activation.Nature communications · 2024Article
- Cellular and molecular characteristics of the premetastatic niches.Animal models and experimental medicine · 2023Review
- Obesity and prostate cancer - microenvironmental roles of adipose tissue.Nature reviews. Urology · 2023Review
- Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma.Nature communications · 2023Article
- Article
- A synthetic lethal screen for Snail-induced enzalutamide resistance identifies JAK/STAT signaling as a therapeutic vulnerability in prostate cancer.Frontiers in molecular biosciences · 2023Article
- Prostate cancer induced bone pain: pathobiology, current treatments and pain responses from recent clinical trials.Discover oncology · 2022Review
- Capecitabine inhibits epithelial-to-mesenchymal transition and proliferation of colorectal cancer cells by mediating the RANK/RANKL pathway.Oncology letters · 2022Article
- A Tailored Approach for Appendicular Impending and Pathologic Fractures in Solid Cancer Metastases.Cancers · 2022Review
- Receptor-interacting protein kinase 2 (RIPK2) stabilizes c-Myc and is a therapeutic target in prostate cancer metastasis.Nature communications · 2022Article
- KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway.Breast cancer research : BCR · 2022Article
- Inhibition of GATA2 in prostate cancer by a clinically available small molecule.Endocrine-related cancer · 2021Article
- Review
- Prostate Cancer Dormancy and Reactivation in Bone Marrow.Journal of clinical medicine · 2021Review
- Cleavage of the Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex by Matrix Metalloproteinase 7/Matrilysin Triggers Prostate Cancer Cell Dyscohesion and Migration.International journal of molecular sciences · 2021Article
- Role of Runx2 in prostate development and stem cell function.The Prostate · 2021Article
- Characteristics of pre-metastatic niche: the landscape of molecular and cellular pathways.Molecular biomedicine · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Prostate cancer (PCa) metastasis to bone is lethal and there is no adequate animal model for studying the mechanisms underlying the metastatic process. Here, we report that receptor activator of NF-κB ligand (RANKL) expressed by PCa cells consistently induced colonization or metastasis to bone in animal models. RANK-mediated signaling established a premetastatic niche through a feed-forward loop, involving the induction of RANKL and c-Met, but repression of androgen receptor (AR) expression and AR signaling pathways. Site-directed mutagenesis and transcription factor (TF) deletion/interference assays identified common TF complexes, c-Myc/Max, and AP4 as critical regulatory nodes. RANKL-RANK signaling activated a number of master regulator TFs that control the epithelial-to-mesenchymal transition (Twist1, Slug, Zeb1, and Zeb2), stem cell properties (Sox2, Myc, Oct3/4, and Nanog), neuroendocrine differentiation (Sox9, HIF1α, and FoxA2), and osteomimicry (c-Myc/Max, Sox2, Sox9, HIF1α, and Runx2). Abrogating RANK or its downstream c-Myc/Max or c-Met signaling network minimized or abolished skeletal metastasis in mice. RANKL-expressing LNCaP cells recruited and induced neighboring non metastatic LNCaP cells to express RANKL, c-Met/activated c-Met, while downregulating AR expression. These initially non-metastatic cells, once retrieved from the tumors, acquired the potential to colonize and grow in bone. These findings identify a novel mechanism of tumor growth in bone that involves tumor cell reprogramming via RANK-RANKL signaling, as well as a form of signal amplification that mediates recruitment and stable transformation of non-metastatic bystander dormant cells.
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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.