ArticleInternational journal of oncology2021
Matrix metalloproteinase‑1 expression is regulated by HIF‑1‑dependent and epigenetic mechanisms and serves a tumor‑suppressive role in gastric cancer progression.
Article in International journal of oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Cumulative evidence for associations between matrix metalloproteinase-1, -3 and -8 variants and cancer risk.Oncology letters · 2026Article
- Hyperglycaemia-Induced Metabolic Stress Promotes EMT-Driven Therapeutic Resistance in Cancer: Evidence of a Deleterious Feed-Forward Cycle.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Kaempferol Inhibits MMP-1-Mediated Migration and Invasion in Gemcitabine-Resistant Pancreatic Cancer Cells.Nutrients · 2026Article
- Single-cell multi-omics characterize colorectal tumors, adjacent healthy tissue and matched (tumor) organoids identifying CRC-unique features.International journal of cancer · 2025Article
- Putative Role of Fatty Acid Metabolic Therapy Using Ketogenic Diet and HIF-1α Inhibition in Hepatocellular Carcinoma: Evidence from an In Vitro Study.International journal of molecular sciences · 2025Article
- Prognostic Significance ofBiology · 2025Article
- Oxygen-Mediated Molecular Mechanisms Involved in Intestinal Ischemia and Reperfusion Injury.International journal of molecular sciences · 2025Review
- Tumor hypoxia shapes natural killer cell anticancer activities.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Review
- Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury.Clinical and translational medicine · 2025Review
- Exploring the mechanism of Synechococcus sp. XM-24 in gastric cancer treatment via network pharmacology and molecular docking.PloS one · 2025Article
- Exploring the anti-metastatic potential of sunitinib and novel analogs in colorectal cancer: insights into HIF-1α mediated metastasis.Frontiers in pharmacology · 2025Article
- Therapeutic Targeting of Hypoxia-Inducible Factors in Cancer.International journal of molecular sciences · 2024Review
- Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy.Frontiers in oncology · 2024Review
- Review
- A HIF-1α inhibitor combined with palmitic acid and L-carnitine treatment can prevent the fat metabolic reprogramming under hypoxia and induce apoptosis in hepatocellular carcinoma cells.Cancer & metabolism · 2023Article
- Hypoxic Effects on Matrix Metalloproteinases' Expression in the Tumor Microenvironment and Therapeutic Perspectives.International journal of molecular sciences · 2023Review
- Article
- Suppression of NASH-Related HCC by Farnesyltransferase Inhibitor through Inhibition of Inflammation and Hypoxia-Inducible Factor-1α Expression.International journal of molecular sciences · 2023Article
- The Expression of MMP1 and MMP7 in Mice Liver after Exposure to Aflatoxin B1 Using Immunohistochemistry Technique.Archives of Razi Institute · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The matrix metalloproteinase (MMP) family is associated with degradation of the extracellular matrix and is known to promote cancer invasion. The present study aimed to investigate the biological role of MMP‑1 in gastric cancer cells and analyze the association between MMP‑1 expression and the clinical outcomes of gastric cancer patients. In the present study, hypoxia accelerated invasion, accompanied by elevated MMP‑1 expression in the gastric cancer cell line 58As9. Additionally, hypoxia‑inducible factor‑1α (HIF‑1α) knockdown in 58As9 cells reduced MMP‑1 expression under hypoxic conditions. Treatment with 5‑aza‑2‑deoxycytidine and trichostatin A restored MMP‑1 expression in the MMP‑1‑deficient cell lines MKN45 and MKN74. These results indicated that MMP‑1 expression was controlled by both HIF‑1α‑dependent and epigenetic mechanisms in gastric cancer cell lines. In addition, MMP‑1 knockdown impaired the hypoxia‑induced invasiveness of 58As9 cells, implicating MMP‑1 in the elevated invasion. By contrast, knockdown enhanced the proliferative ability of 58As9 cells, whereby expression of cell cycle‑related genes was subsequently altered. In nude mouse models, the knockdown accelerated the growth of xenograft tumor and the development of peritoneal dissemination. In an immunohistochemical study using 161 surgically resected cancer tissues, the Ki67 score was significantly higher in the group with low MMP‑1 expression (P<0.001). Disease‑free survival (DFS) and disease‑specific survival (DSS) were both significantly reduced in patients with low MMP‑1 expression (log‑rank test; DFS: P=0.005; DSS: P=0.022). Multivariate analysis demonstrated that MMP‑1 expression was an independent prognostic factor for DFS and DSS [DFS: HR=2.11 (1.22‑3.92) P=0.005, DSS: HR=2.90 (1.23‑8.50) P=0.012]. In conclusion, the present study indicated that MMP‑1 may serve as a tumor‑suppressive factor that inhibits gastric cancer progression, although it promoted invasion
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