ArticlePloS one2013
In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly.World journal of gastroenterology · 2023Pooled it
- The Role of the Metzincin Superfamily in Prostate Cancer Progression: A Systematic-Like Review.International journal of molecular sciences · 2021Pooled it
- ADAM9 in tumor biology: molecular functions, clinical implications, and therapeutic targeting.Cellular & molecular biology letters · 2026Review
- Association of ADAM family members with proliferation signaling and disease progression in multiple myeloma.Blood cancer journal · 2024Article
- An Antibody of the Secreted Isoform of Disintegrin and Metalloprotease 9 (sADAM9) Inhibits Epithelial-Mesenchymal Transition and Migration of Prostate Cancer Cell Lines.International journal of molecular sciences · 2024Article
- Melatonin improves muscle injury and differentiation by increasing Pax7 expression.International journal of biological sciences · 2023Article
- Article
- HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism.Cells · 2022Article
- The ADAM9/UBN2/AKR1C3 axis promotes resistance to androgen-deprivation in prostate cancer.American journal of cancer research · 2022Article
- REG4 promotes the proliferation and anti-apoptosis of cancer.Frontiers in cell and developmental biology · 2022Review
- Clinicopathological Significance and Prognostic Implications of REG4 Immunohistochemical Expression in Colorectal Cancer.Medicina (Kaunas, Lithuania) · 2021Article
- Stabilization of ADAM9 by N-α-acetyltransferase 10 protein contributes to promoting progression of androgen-independent prostate cancer.Cell death & disease · 2020Article
- Molecular mechanisms and clinical management of cancer bone metastasis.Bone research · 2020Review
- The Clinical Significance and Mechanisms of REG4 in Human Cancers.Frontiers in oncology · 2020Review
- REG4 is an indicator for KRAS mutant lung adenocarcinoma with TTF-1 low expression.Journal of cancer research and clinical oncology · 2019Article
- Bone Marrow Mesenchymal Stem Cell-Derived Exosomal MicroRNA-126-3p Inhibits Pancreatic Cancer Development by Targeting ADAM9.Molecular therapy. Nucleic acids · 2019Article
- Regulatory signaling network in the tumor microenvironment of prostate cancer bone and visceral organ metastases and the development of novel therapeutics.Asian journal of urology · 2019Review
- The pleiotropic roles of ADAM9 in the biology of solid tumors.Cellular and molecular life sciences : CMLS · 2018Review
- Reactive oxygen species-mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression.Scientific reports · 2017Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM) 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA) significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4) expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21(Cip1/WAF1), which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer.
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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.