ArticleThe FEBS journal2019
A mitochondrial ROS pathway controls matrix metalloproteinase 9 levels and invasive properties in RAS-activated cancer cells.
Article in The FEBS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 85 citations in OpenAlex.
- Photoreceptor-targeted engineered exosomes encapsulating black phosphorus quantum dots for alleviating photoreceptor degeneration.Journal of nanobiotechnology · 2026Article
- The Pro-Metastatic Roles of ROS.Antioxidants (Basel, Switzerland) · 2026Review
- Multi-omics mapping identifies CYBA-mediated mitochondrial dysfunction driving macrophage polarization and ferroptosis via Nrf2 pathway in atherosclerosis.APL bioengineering · 2026Article
- Priming of human monocytes by β-glucan and obesity-associated factors: modifications to global DNA methylation, gene expression, phenotype and function.Frontiers in immunology · 2026Article
- Gut-heart axis disruption and LPS translocation: driving atrial fibrillation through inflammatory storm and fibrotic mechanisms.Frontiers in endocrinology · 2026Review
- Interplay of oxidative stress and antioxidant mechanisms in cancer development and progression.Archives of toxicology · 2026Review
- Hic-5 drives epithelial mechanotransduction promoting a feed-forward cycle of bronchoconstriction.Nature communications · 2025Article
- Article
- Understanding the complexity of tumor-associated macrophages: Druggable and therapeutic insights.Acta pharmaceutica Sinica. B · 2025Review
- Reactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics.Cells · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Based exploration of the diagnostic value of oxidative stress-related key genes in chronic obstructive pulmonary disease.Cell biology and toxicology · 2025Article
- Activating transcription factor 3 induces oxidative stress and genotoxicity, transcriptionally modulating metastasis-related gene expression in human papillomavirus-infected cervical cancer.Virology journal · 2025Article
- Mitochondrial Dysfunction and Its Potential Molecular Interplay in Hypermobile Ehlers-Danlos Syndrome: A Scoping Review Bridging Cellular Energetics and Genetic Pathways.Current issues in molecular biology · 2025Review
- Polyoxometalate-based injectable coacervate inhibits HCC metastasis after incomplete radiofrequency ablation via scavenging ROS.Journal of nanobiotechnology · 2025Article
- Acute Three-Dimensional Hypoxia Regulates Angiogenesis.Advanced healthcare materials · 2025Article
- Regulation of anti-tumour effects of Paris polyphylla saponins via ROS: molecular mechanisms and therapeutic potentials.Frontiers in pharmacology · 2025Review
- Recent advances in reactive oxygen species (ROS)-responsive drug delivery systems for photodynamic therapy of cancer.Acta pharmaceutica Sinica. B · 2024Review
- Insights from a multiscale framework on metabolic rate variation driving glioblastoma multiforme growth and invasion.Communications engineering · 2024Article
- Oxidative Stress and Age-Related Tumors.Antioxidants (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matrix metalloproteinases (MMPs) are tissue-remodeling enzymes involved in the processing of various biological molecules. MMPs also play important roles in cancer metastasis, contributing to angiogenesis, intravasation of tumor cells, and cell migration and invasion. Accordingly, unraveling the signaling pathways controlling MMP activities could shed additional light on cancer biology. Here, we report a molecular axis, comprising the molecular adaptor hydrogen peroxide-inducible clone-5 (HIC-5), NADPH oxidase 4 (NOX4), and mitochondria-associated reactive oxygen species (mtROS), that regulates MMP9 expression and may be a target to suppress cancer metastasis. We found that this axis primarily downregulates mtROS levels which stabilize MMP9 mRNA. Specifically, HIC-5 suppressed the expression of NOX4, the source of the mtROS, thereby decreasing mtROS levels and, consequently, destabilizing MMP9 mRNA. Interestingly, among six cancer cell lines, only EJ-1 and MDA-MB-231 cells exhibited upregulation of NOX4 and MMP9 expression after shRNA-mediated HIC-5 knockdown. In these two cell lines, activating RAS mutations commonly occur, suggesting that the HIC-5-mediated suppression of NOX4 depends on RAS signaling, a hypothesis that was supported experimentally by the introduction of activated RAS into mammary epithelial cells. Notably, HIC-5 knockdown promoted lung metastasis of MDA-MB-231 cancer cells in mice. The tumor growth of HIC-5-silenced MDA-MB-231 cells at the primary sites was comparable to that of control cells. Consistently, the invasive properties of the cells, but not their proliferation, were enhanced by the HIC-5 knockdown in vitro. We conclude that NOX4-mediated mtROS signaling increases MMP9 mRNA stability and affects cancer invasiveness but not tumor growth.
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