ArticleOncogene2010
Src family kinase/abl inhibitor dasatinib suppresses proliferation and enhances differentiation of osteoblasts.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The trial behind it
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
41 citing papers in PubMed, 80 citations in OpenAlex.
- Whole-Body [Tomography (Ann Arbor, Mich.) · 2021Trial
- Castration-resistant prostate cancer bone metastasis response measured by 18F-fluoride PET after treatment with dasatinib and correlation with progression-free survival: results from American College of Radiology Imaging Network 6687.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2015Trial
- A randomized phase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients.Investigational new drugs · 2014Trial
- Article
- Dasatinib regulates the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals.International journal of medical sciences · 2023Article
- Bone marrow niches in the regulation of bone metastasis.British journal of cancer · 2021Review
- Article
- Exosomes from Placenta-Derived Mesenchymal Stem Cells Are Involved in Liver Regeneration in Hepatic Failure Induced by Bile Duct Ligation.Stem cells international · 2020Article
- Cell-based RNAi screening and high-content analysis in primary calvarian osteoblasts applied to identification of osteoblast differentiation regulators.Scientific reports · 2018Article
- The Osteoclast in Bone Metastasis: Player and Target.Cancers · 2018Review
- Bone-targeted agents in multiple myeloma.Hematology reports · 2018Article
- BIGH3 Promotes Osteolytic Lesions in Renal Cell Carcinoma Bone Metastasis by Inhibiting Osteoblast Differentiation.Neoplasia (New York, N.Y.) · 2018Article
- Cabozantinib-induced osteoblast secretome promotes survival and migration of metastatic prostate cancer cells in bone.Oncotarget · 2017Article
- The Src family kinase inhibitor dasatinib delays pain-related behaviour and conserves bone in a rat model of cancer-induced bone pain.Scientific reports · 2017Article
- Multiparameter Analysis of Off-Target Effects of Dasatinib on Bone Homeostasis in Patients With Newly Diagnosed Chronic Myelogenous Leukemia.Clinical lymphoma, myeloma & leukemia · 2016Article
- SRC kinase inhibition with saracatinib limits the development of osteolytic bone disease in multiple myeloma.Oncotarget · 2016Article
- Characterization of anti-leukemia components from Indigo naturalis using comprehensive two-dimensional K562/cell membrane chromatography and in silico target identification.Scientific reports · 2016Article
- Secretome analysis of an osteogenic prostate tumor identifies complex signaling networks mediating cross-talk of cancer and stromal cells within the tumor microenvironment.Molecular & cellular proteomics : MCP · 2015Article
- c-Abl tyrosine kinase promotes adipocyte differentiation by targeting PPAR-gamma 2.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Autophagy as a modulator and target in prostate cancer.Nature reviews. Urology · 2014Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Dasatinib, a dual Src family kinase and Abl inhibitor, is being tested clinically for the treatment of prostate cancer bone metastasis. Bidirectional interactions between osteoblasts and prostate cancer cells are critical in the progression of prostate cancer in bone, but the effect of dasatinib on osteoblasts is unknown. We found that dasatinib inhibited proliferation of primary mouse osteoblasts isolated from mouse calvaria and the immortalized MC3T3-E1 cell line. In calvarial osteoblasts from Col-luc transgenic mice carrying osteoblast-specific Col1alpha1 promoter reporter, luciferase activity was inhibited. Dasatinib also inhibited fibroblast growth factor-2-induced osteoblast proliferation, but strongly promoted osteoblast differentiation, as reflected by stimulation of alkaline phosphatase activity, osteocalcin secretion and osteoblast mineralization. To determine how dasatinib blocks proliferative signaling in osteoblasts, we analyzed the expression of a panel of tyrosine kinases, including Src, Lyn, Fyn, Yes and Abl, in osteoblasts. In the Src family kinases, only Src was activated at a high level. Abl was expressed at a low level in osteoblasts. Phosphorylation of Src-Y419 or Abl-Y245 was inhibited by dasatinib treatment. Knockdown of either Src or Abl by lenti-shRNA in osteoblasts enhances osteoblast differentiation, suggesting that dasatinib enhances osteoblast differentiation through inhibition of both Src and Abl.
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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.