ArticleOncogene2014
A gene signature of bone metastatic colonization sensitizes for tumor-induced osteolysis and predicts survival in lung cancer.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Lactylation-related lncRNAs can forecast prognosis and immune response of lung adenocarcinoma.Discover oncology · 2025Article
- PITX1 as a grading, prognostic and tumor-infiltrating immune cells marker for chondrosarcoma: a public database-based immunoassay and tissue sample analysis.Frontiers in oncology · 2025Article
- Clofazimine inhibits small-cell lung cancer progression by modulating the kynurenine/aryl hydrocarbon receptor axis.International journal of biological macromolecules · 2024Article
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- PITX1 plays essential functions in cancer.Frontiers in oncology · 2023Review
- Tumor ENPP1 (CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer.Cancer discovery · 2022Article
- Cellular plasticity in bone metastasis.Bone · 2022Article
- Role of chemokines in hepatocellular carcinoma (Review).Oncology reports · 2021Review
- Different roles of matrix metalloproteinase 2 in osteolysis of skeletal dysplasia and bone metastasis (Review).Molecular medicine reports · 2021Review
- MiRNAs and LncRNAs: Dual Roles in TGF-β Signaling-Regulated Metastasis in Lung Cancer.International journal of molecular sciences · 2020Review
- Identification of DHX36 as a tumour suppressor through modulating the activities of the stress-associated proteins and cyclin-dependent kinases in breast cancer.American journal of cancer research · 2020Article
- 27-Hydroxycholesterol enhanced osteoclastogenesis in lung adenocarcinoma microenvironment.Journal of cellular physiology · 2019Article
- Tumor-derived exosomes promote the in vitro osteotropism of melanoma cells by activating the SDF-1/CXCR4/CXCR7 axis.Journal of translational medicine · 2019Article
- Macrophage Origin, Metabolic Reprogramming and IL-1 Signaling: Promises and Pitfalls in Lung Cancer.Cancers · 2019Review
- Bone Metastasis: Find Your Niche and Fit in.Trends in cancer · 2019Review
- Blockade of the Complement C5a/C5aR1 Axis Impairs Lung Cancer Bone Metastasis by CXCL16-mediated Effects.American journal of respiratory and critical care medicine · 2018Article
- Differentially expressed and survival-related proteins of lung adenocarcinoma with bone metastasis.Cancer medicine · 2018Article
- Article
- Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway.Scientific reports · 2016Article
- Hedgehog and TGFβ signaling converge on Gli2 to control bony invasion and bone destruction in oral squamous cell carcinoma.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone metastasis of lung adenocarcinoma (AC) is a frequent complication of advanced disease. The purpose of this study was to identify key mediators conferring robust prometastatic activity with clinical significance. We isolated highly metastatic subpopulations (HMS) using a previously described in vivo model of lung AC bone metastasis. We performed transcriptomic profiling of HMS and stringent bioinformatics filtering. Functional validation was assessed by overexpression and lentiviral silencing of single, double and triple combination in vivo and in vitro. We identified HDAC4, PITX1 and ROBO1 that decreased bone metastatic ability after their simultaneous abrogation. These effects were solely linked to defects in osseous colonization. The molecular mechanisms related to bone colonization were mediated by non-cell autonomous effects that include the following: (1) a marked decrease in osteoclastogenic activity in vitro and in vivo, an effect associated with reduced pro-osteoclastogenic cytokines IL-11 and PTHrP expression levels, as well as decreased in vitro expression of stromal rankl in conditions mimicking tumor-stromal interactions; (2) an abrogated response to TGF-β signaling by decreased phosphorylation and levels of Smad2/3 in tumor cells and (3) an impaired metalloproteolytic activity in vitro. Interestingly, coexpression of HDAC4 and PITX1 conferred high prometastatic activity in vivo. Further, levels of both genes correlated with patients at higher risk of metastasis in a clinical lung AC data set and with a poorer clinical outcome. These findings provide functional and clinical evidence that this metastatic subset is an important determinant of osseous colonization. These data suggest novel therapeutic targets to effectively block lung AC 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.