ArticleOncogene2010
Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- ADAM Proteases in Cancer: Biological Roles, Therapeutic Challenges, and Emerging Opportunities.Cancers · 2025Review
- Unraveling the alterations and biomarkers in the tumor microenvironment in lung adenocarcinoma metastases and their indications for therapeutic response and prognosis.Therapeutic advances in medical oncology · 2025Review
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
- USP15 negatively regulates lung cancer progression through the TRAF6-BECN1 signaling axis for autophagy induction.Cell death & disease · 2022Article
- Roles of the RANKL-RANK Axis in Immunity-Implications for Pathogenesis and Treatment of Bone Metastasis.Frontiers in immunology · 2022Review
- Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer.Bioengineered · 2021Article
- Influence of Genetic Background and Sex on Gene Expression in the Mouse (Comparative medicine · 2020Article
- 27-Hydroxycholesterol enhanced osteoclastogenesis in lung adenocarcinoma microenvironment.Journal of cellular physiology · 2019Article
- Macrophage Origin, Metabolic Reprogramming and IL-1 Signaling: Promises and Pitfalls in Lung Cancer.Cancers · 2019Review
- Salt-Mediated Nanopore Detection of ADAM-17.ACS applied bio materials · 2019Article
- Complement in Metastasis: A Comp in the Camp.Frontiers in immunology · 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
- Intervertebral Disc Degeneration in a Percutaneous Mouse Tail Injury Model.American journal of physical medicine & rehabilitation · 2018Article
- The Many Facets of Metzincins and Their Endogenous Inhibitors: Perspectives on Ovarian Cancer Progression.International journal of molecular sciences · 2018Review
- Fine Tuning Cell Migration by a Disintegrin and Metalloproteinases.Mediators of inflammation · 2017Review
- microRNA-590 suppresses the tumorigenesis and invasiveness of non-small cell lung cancer cells by targeting ADAM9.Molecular and cellular biochemistry · 2016Article
- ADAM8 as a drug target in pancreatic cancer.Nature communications · 2015Article
- N-glycosylation regulates ADAM8 processing and activation.The Journal of biological chemistry · 2014Article
- A gene signature of bone metastatic colonization sensitizes for tumor-induced osteolysis and predicts survival in lung cancer.Oncogene · 2014Article
- Expression of A disintegrin and metalloprotease 8 is associated with cell growth and poor survival in colorectal cancer.BMC cancer · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ADAMs (a disintegrin and metalloprotease) are transmembrane proteins involved in a variety of physiological processes and tumorigenesis. Recently, ADAM8 has been associated with poor prognosis of lung cancer. However, its contribution to tumorigenesis in the context of lung cancer metastasis remains unknown. Native ADAM8 expression levels were lower in lung cancer cell lines. In contrast, we identified and characterized two novel spliced isoforms encoding truncated proteins, Delta18a and Delta14', which were present in several tumor cell lines and not in normal cells. Overexpression of Delta18a protein resulted in enhanced invasive activity in vitro. ADAM8 and its Delta14' isoform expression levels were markedly increased in lung cancer cells, in conditions mimicking tumor microenvironment. Moreover, addition of supernatants from Delta14'-overexpressing cells resulted in a significant increase in tartrate-resistant acid phosphatase+ cells in osteoclast cultures in vitro. These findings were associated with increased pro-osteoclastogenic cytokines interleukin (IL)-8 and IL-6 protein levels. Furthermore, lung cancer cells overexpressing Delta14' increased prometastatic activity with a high tumor burden and increased osteolysis in a murine model of bone metastasis. Thus, the expression of truncated forms of ADAM8 by the lung cancer cells may result in the specific upregulation of their invasive and osteoclastogenic activities in the bone microenvironment. These findings suggest a novel mechanism of tumor-induced osteolysis in metastatic bone colonization.
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