ArticleNeoplasia (New York, N.Y.)2009
Regulation of membrane-type 4 matrix metalloproteinase by SLUG contributes to hypoxia-mediated metastasis.
Article in Neoplasia (New York, N.Y.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review.Molecular cancer · 2019Pooled it
- Spiny Mice Show a Profibrotic Epicardial Mesothelial Response to Hypoxic Injury Comparable to C57BL/6 Mice.Biomolecules · 2026Article
- Photodynamic Therapy Targeting Matrix Metalloproteases in Cancer: Standpoint for an Innovative Anticancer Strategy.Current issues in molecular biology · 2026Review
- Oxygen-Mediated Molecular Mechanisms Involved in Intestinal Ischemia and Reperfusion Injury.International journal of molecular sciences · 2025Review
- Geographic Variation in Epigenetic Responses to Hypoxia in Deer Mice (Peromyscus maniculatus) Distributed Along an Elevational Gradient.Molecular ecology · 2025Article
- SIRT1 in acute lung injury: unraveling its pleiotropic functions and therapeutic development prospects.Molecular and cellular biochemistry · 2025Review
- Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury.Clinical and translational medicine · 2025Review
- Review
- A new perspective on the therapeutic potential of tumor metastasis: targeting the metabolic interactions between TAMs and tumor cells.International journal of biological sciences · 2024Review
- Impact of cell plasticity on prostate tumor heterogeneity and therapeutic response.American journal of clinical and experimental urology · 2024Review
- Hypoxic Effects on Matrix Metalloproteinases' Expression in the Tumor Microenvironment and Therapeutic Perspectives.International journal of molecular sciences · 2023Review
- SLUG and SNAIL as Potential Immunohistochemical Biomarkers for Renal Cancer Staging and Survival.International journal of molecular sciences · 2023Article
- Molecular Mechanisms Driven by MT4-MMP in Cancer Progression.International journal of molecular sciences · 2023Review
- Elevated Plasma Levels of MT4-MMP and MT6-MMP; A New Observation in Patients with Thyroid Nodules.Archives of Iranian medicine · 2023Article
- Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors HarboringCancer research communications · 2023Article
- Article
- Dynamic EMT: a multi-tool for tumor progression.The EMBO journal · 2021Review
- Epithelial-Mesenchymal Transition Associated with Head and Neck Squamous Cell Carcinomas: A Review.Cancers · 2021Review
- The roles of extracellular vesicles in the development, microenvironment, anticancer drug resistance, and therapy of head and neck squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- Targeting ferroptosis for cancer therapy: iron metabolism and anticancer immunity.American journal of cancer research · 2021Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hypoxic tumor environment has been shown to be critical to cancer metastasis through the promotion of angiogenesis, induction of epithelial-mesenchymal transition (EMT), and acquisition of invasive potential. However, the impact of hypoxia on the expression profile of the proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP) is a glycosyl-phosphatidyl inositol-anchored protease that has been shown to be overexpressed in human cancers. However, detailed mechanisms regarding the regulation and function of MT4-MMP expression in tumor cells remain unknown. Here, we demonstrate that hypoxia or overexpression of hypoxia-inducible factor-1alpha (HIF-1alpha) induced MT4-MMP expression in human cancer cells. Activation of SLUG, a transcriptional factor regulating the EMT process of human cancers, by HIF-1alpha was critical for the induction of MT4-MMP under hypoxia. SLUG regulated the transcription of MT4-MMP through direct binding to the E-box located in its proximal promoter. Short-interference RNA-mediated knockdown of MT4-MMP attenuated in vitro invasiveness and in vivo pulmonary colonization of tumor cells without affecting cell migratory ability. MT4-MMP promoted invasiveness and pulmonary colonization through modulation of the expression profile of MMPs and angiogenic factors. Finally, coexpression of HIF-1alpha and MT4-MMP in human head and neck cancer was predictive of a worse clinical outcome. These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer 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.