ArticleThe Journal of clinical investigation2014
DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast cancer bone metastasis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 74 citations in OpenAlex.
- Trial
- ACE2 and Parkinsonism‑related bone metabolic alterations: signaling pathways and hub gene analysis.Molecular genetics and genomics : MGG · 2026Article
- Opposing effects of Rho-associated coiled-coil kinase 1 (ROCK1) and ROCK2 in TGF-β-SMAD signaling.Cell communication and signaling : CCS · 2026Article
- Review
- [Overexpression of parathyroid hormone-like hormone facilitates hepatocellular carcinoma progression and correlates with adverse outcomes].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence.Oncogene · 2024Article
- Ononin Inhibits Tumor Bone Metastasis and Osteoclastogenesis By Targeting Mitogen-Activated Protein Kinase Pathway in Breast Cancer.Research (Washington, D.C.) · 2024Article
- Predictive and prognostic biomarkers of bone metastasis in breast cancer: current status and future directions.Cell & bioscience · 2023Review
- Metastasis prevention with bone-targeted agents: a complex interaction between the microenvironment and tumour biology.Journal of bone and mineral metabolism · 2023Review
- IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer.The Journal of clinical investigation · 2022Article
- Article
- Aberrant activation of TGF-β1 induces high bone turnoverFrontiers in endocrinology · 2022Article
- DLC1 inhibits colon adenocarcinoma cell migration by promoting secretion of the neurotrophic factor MANF.Frontiers in oncology · 2022Article
- Deregulated molecules and pathways in the predisposition and dissemination of breast cancer cells to bone.Computational and structural biotechnology journal · 2022Article
- Interaction Between Serum/Glucocorticoid-Regulated Kinase 1 and Interleukin-6 in Chronic Rhinosinusitis.Allergy, asthma & immunology research · 2021Article
- Fascin Inhibitors Decrease Cell Migration and Adhesion While Increase Overall Survival of Mice Bearing Bladder Cancers.Cancers · 2021Article
- Review
- CST6 protein and peptides inhibit breast cancer bone metastasis by suppressing CTSB activity and osteoclastogenesis.Theranostics · 2021Article
- Curcumin inhibits the growth of triple-negative breast cancer cells by silencing EZH2 and restoring DLC1 expression.Journal of cellular and molecular medicine · 2020Article
- Anti-Metastasis Fascin Inhibitors Decrease the Growth of Specific Subtypes of Cancers.Cancers · 2020Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone metastasis is a frequent complication of breast cancer that is often accelerated by TGF-β signaling; however, little is known about how the TGF-β pathway is regulated during bone metastasis. Here we report that deleted in liver cancer 1 (DLC1) is an important regulator of TGF-β responses and osteolytic metastasis of breast cancer cells. In murine models, breast cancer cells lacking DLC1 expression exhibited enhanced capabilities of bone metastasis. Knockdown of DLC1 in cancer cells promoted bone metastasis, leading to manifested osteolysis and accelerated death in mice, while DLC1 overexpression suppressed bone metastasis. Activation of Rho-ROCK signaling in the absence of DLC1 mediated SMAD3 linker region phosphorylation and TGF-β-induced expression of parathyroid hormone-like hormone (PTHLH), leading to osteoclast maturation for osteolytic colonization. Furthermore, pharmacological inhibition of Rho-ROCK effectively reduced PTHLH production and breast cancer bone metastasis in vitro and in vivo. Evaluation of clinical breast tumor samples revealed that reduced DLC1 expression was linked to elevated PTHLH expression and organ-specific metastasis to bone. Overall, our findings define a stroma-dependent paradigm of Rho signaling in cancer and implicate Rho-TGF-β crosstalk in osteolytic bone metastasis.
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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.