ArticleThe Journal of biological chemistry2019
S100A4 alters metabolism and promotes invasion of lung cancer cells by up-regulating mitochondrial complex I protein NDUFS2.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Circulating proteins associated with histological subtypes of lung cancer from genetic and population-based perspectives.PLoS genetics · 2025Pooled it
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- Article
- Mitochondrial complex I in focus: mechanisms and therapeutic strategies of urinary system diseases.Frontiers in physiology · 2026Review
- Extracellular vesicles modulate integrin signaling and subcellular energetics to promote pulmonary lymphangioleiomyomatosis metastasis.Communications biology · 2025Article
- MicroRNA-125b-5p Drives MMP-2 Expression via Activation of RAGE-38MAPK-p65/p50NF-κB Axis: A Novel Mechanism in Human Lung Cancer Cells.International journal of molecular sciences · 2025Article
- Relationship of S100 Proteins with Neuroinflammation.Biomolecules · 2025Review
- Integrated Analysis of Lactate-Related Genes Identifies S100A4 as a Novel Marker Promoting the Migration and Invasion of Endometrial Stromal Cell in Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 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
- Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A review on clinical implications of S100 proteins in lung diseases.Frontiers in medicine · 2025Review
- Identification of an Ara-C resistance-related gene risk score and the role of S100A4 in AML via NR6A1-dependent activation and p53 regulation.Frontiers in pharmacology · 2025Article
- S100 Protein Family in Lung Cancer: an Updated Narrative Review.Cancer management and research · 2025Review
- Identification of DAP3 as candidate prognosis marker and potential therapeutic target for hepatocellular carcinoma.Frontiers in immunology · 2025Article
- The role of mitochondria in tumor metastasis and advances in mitochondria-targeted cancer therapy.Cancer metastasis reviews · 2024Review
- Exploring Aerobic Energy Metabolism in Breast Cancer: A Mutational Profile of Glycolysis and Oxidative Phosphorylation.International journal of molecular sciences · 2024Article
- Mitochondria: a new intervention target for tumor invasion and metastasis.Molecular medicine (Cambridge, Mass.) · 2024Review
- OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death.Cell death discovery · 2024Article
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Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
It is generally accepted that alterations in metabolism are critical for the metastatic process; however, the mechanisms by which these metabolic changes are controlled by the major drivers of the metastatic process remain elusive. Here, we found that S100 calcium-binding protein A4 (S100A4), a major metastasis-promoting protein, confers metabolic plasticity to drive tumor invasion and metastasis of non-small cell lung cancer cells. Investigating how S100A4 regulates metabolism, we found that S100A4 depletion decreases oxygen consumption rates, mitochondrial activity, and ATP production and also shifts cell metabolism to higher glycolytic activity. We further identified that the 49-kDa mitochondrial complex I subunit NADH dehydrogenase (ubiquinone) Fe-S protein 2 (NDUFS2) is regulated in an S100A4-dependent manner and that S100A4 and NDUFS2 exhibit co-occurrence at significant levels in various cancer types as determined by database-driven analysis of genomes in clinical samples using cBioPortal for Cancer Genomics. Importantly, we noted that S100A4 or NDUFS2 silencing inhibits mitochondrial complex I activity, reduces cellular ATP level, decreases invasive capacity in three-dimensional growth, and dramatically decreases metastasis rates as well as tumor growth
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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.