ArticleOncogene2004
Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 270 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
270 citing papers in PubMed, 3 syntheses or guidelines pooled it, 553 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- A Systematic Review to Clarify the Prognostic Values of CD44 and CD44Frontiers in oncology · 2021Pooled it
- Clinicopathological and Prognostic Role of STAT3/p-STAT3 in Breast Cancer Patients in China: A Meta-Analysis.Scientific reports · 2019Pooled it
- Investigation of exercise-mimetic bioactive molecules as modulators of MMP activity and expression in cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Loss of cold shock domain-containing protein E1 (CSDE1) function enhances mRNA stability of interleukin-6 and promotes malignant transformation in endometrial cancer cells.Cell communication and signaling : CCS · 2026Article
- JAK/STAT3 axis in breast cancer: opportunities for intervention with natural phytochemical-based nanotherapeutics.Medical oncology (Northwood, London, England) · 2026Review
- Aging modulation of the immune system and immunotherapy efficacy in cancer.Frontiers in immunology · 2026Review
- Reduction in the hepatocellular carcinoma antioncogeneWorld journal of gastrointestinal surgery · 2025Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- JAK-STAT Signaling in Autoimmunity and Cancer.ImmunoTargets and therapy · 2025Review
- Risk Prediction of Colon Cancer Metastasis and Bioinformatics Analysis of Aspirin Treatment.International journal of genomics · 2025Article
- Empagliflozin in Acute Myocardial Infarction Reduces No-Reflow and Preserves Cardiac Function by Preventing Endothelial Damage.JACC. Basic to translational science · 2025Article
- Nano-Drug Delivery Systems Targeting MMPs: A Promising Treatment for Gliomas.International journal of nanomedicine · 2025Review
- Synthetic Protein-to-DNA Input Exchange for Protease Activity Detection Using CRISPR-Cas12a.Analytical chemistry · 2024Article
- Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation.Cancers · 2024Review
- Combined effects of naringin and doxorubicin on the JAK/STAT signaling pathway reduce the development and spread of breast cancer cells.Scientific reports · 2024Article
- Exploring Novel Frontiers: Leveraging STAT3 Signaling for Advanced Cancer Therapeutics.Cancers · 2024Review
- Experimental evidence for anti-metastatic actions of apigenin: a mini review.Frontiers in oncology · 2024Review
- PCBP1 regulates LIFR through FAM3C to maintain breast cancer stem cell self-renewal and invasiveness.Cancer biology & therapy · 2023Article
- Oligonucleotide-Based Therapeutics for STAT3 Targeting in Cancer-Drug Carriers Matter.Cancers · 2023Review
210 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
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of matrix metalloproteinase-2 (MMP-2) has been linked with tumor invasion, angiogenesis, and metastasis. However, the molecular basis for MMP-2 overexpression in tumor cells remains unclear. In this study, by using K-1735 melanoma system, we demonstrated that highly metastatic C4, M2, and X21 tumor cells express elevated MMP-2 mRNA and enzymatic activity, whereas poorly metastatic C10, C19, and C23 tumor cells express much lower levels. Moreover, a concomitant elevated Stat3 activity has been detected in these metastatic tumor cells that overexpress MMP-2. Transfection of constitutively activated Stat3 into poorly metastatic C23 tumor cells directly activated the MMP-2 promoter, whereas the expression of a dominant-negative Stat3 in highly metastatic C4 tumor cells inhibited the MMP-2 promoter. A high-affinity Stat3-binding element was identified in the MMP-2 promoter and Stat3 protein bound directly to the MMP-2 promoter. Blockade of activated Stat3 through expression of a dominant-negative Stat3 significantly suppressed MMP-2 expression in the metastatic tumor cells. Therefore, overexpression of MMP-2 in the metastatic melanoma cells can be attributed to elevated Stat3 activity, and Stat3 upregulates the transcription of MMP-2 through direct interaction with the MMP-2 promoter. Furthermore, blockade of activated Stat3 in highly metastatic C4 cells significantly suppressed the invasiveness of the tumor cells, inhibited tumor growth, and prevented metastasis in nude mice. Collectively, these studies suggest that Stat3 signaling directly regulates MMP-2 expression, tumor invasion, and metastasis, and that Stat3 activation might be a crucial event in the development of metastasis.
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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.