ArticleOncogene2003
Type 1 insulin-like growth factor regulates MT1-MMP synthesis and tumor invasion via PI 3-kinase/Akt signaling.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 148 citations in OpenAlex.
- Decoding the mechanisms behind second primary cancers.Journal of translational medicine · 2025Review
- Targeting the IGF-Axis in Cultured Pediatric High-Grade Glioma Cells Inhibits Cell Cycle Progression and Survival.Pharmaceuticals (Basel, Switzerland) · 2023Article
- TSPAN8 serves as a prognostic marker involving Akt/MAPK pathway in nasopharyngeal carcinoma.Annals of translational medicine · 2019Article
- MT1-MMP downregulation via the PI3K/Akt signaling pathway is required for the mechanical stretching-inhibited invasion of bone-marrow-derived mesenchymal stem cells.Journal of cellular physiology · 2019Article
- A Brief Overview of the Antitumoral Actions of Leelamine.Biomedicines · 2019Review
- Molecular Targets Modulated by Fangchinoline in Tumor Cells and Preclinical Models.Molecules (Basel, Switzerland) · 2018Review
- miR‑448 targets Rab2B and is pivotal in the suppression of pancreatic cancer.Oncology reports · 2018Article
- Collagen IV-conveyed signals can regulate chemokine production and promote liver metastasis.Oncogene · 2018Article
- Bioactive Compounds fromMarine drugs · 2018Article
- Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.Oncotarget · 2018Article
- Regulation of insulin-like growth factor receptors by Ubiquilin1.The Biochemical journal · 2017Article
- Unbalancing p53/Mdm2/IGF-1R axis by Mdm2 activation restrains the IGF-1-dependent invasive phenotype of skin melanoma.Oncogene · 2017Article
- Three-dimensional collagen matrix induces a mechanosensitive invasive epithelial phenotype.Scientific reports · 2017Article
- miR-184 exhibits angiostatic properties via regulation of Akt and VEGF signaling pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway.Oncology letters · 2016Article
- The effects and mechanisms of SLC34A2 in tumorigenesis and progression of human non-small cell lung cancer.Journal of biomedical science · 2015Article
- Human pancreatic cancer stem cells are sensitive to dual inhibition of IGF-IR and ErbB receptors.BMC cancer · 2015Article
- Emerging Role and Targeting of Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) in Human Malignancies.Clinical cancer drugs · 2015Article
- Novel therapeutic targets for pancreatic cancer.World journal of gastroenterology · 2014Review
- Overexpression of muscarinic receptor 3 promotes metastasis and predicts poor prognosis in non-small-cell lung cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The membrane type 1 matrix metalloproteinase (MT1-MMP) has been identified as a major activator of MMP-2 - a process involving the formation of a trimolecular complex with TIMP-2. We previously identified the IGF-I receptor as a positive regulator of MMP-2 synthesis. Here, we investigated the role of IGF-IR in the regulation of MT1-MMP. Highly invasive Lewis lung carcinoma subline H-59 cells express MT1-MMP and utilize it to activate their major extracellular matrix degrading proteinase-MMP-2. These cells were transiently transfected with a plasmid vector expressing a luciferase reporter gene downstream of the mouse MT1-MMP promoter. IGF-I treatment increased luciferase activity in the transfected cells by up to 10-fold and augmented endogenous MT1-MMP mRNA and protein synthesis by up to 2-3-fold, relative to controls. MT1-MMP induction and invasion were blocked by the PI 3-kinase inhibitors LY294002 and wortmannin and by rapamycin, but not by the MEK inhibitor PD98059. Overexpression of a dominant negative Akt mutant or of the tumor suppressor phosphatase and tensin homologue, PTEN, in these cells also caused a significant reduction in MT1-MMP expression and invasion. The results demonstrate that IGF-IR controls tumor cell invasion by coordinately regulating MMP-2 expression and its MT1-MMP-mediated activation and identify PI 3-kinase/Akt/mTOR signaling as critical to this regulation.
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