ArticleNature communications2019
The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Network-based gene deletion analysis identifies candidate genes and molecular mechanism involved in clear cell renal cell carcinoma.Journal of genetics · 2021Pooled it
- 6-Shogaol inhibits HSCs activation and liver fibrosis by regulating glycolytic reprogramming via targeting HIF-1α.Chinese medicine · 2026Article
- Siah2 regulates lipid uptake in adipose tissue macrophages.The Journal of biological chemistry · 2026Article
- SIAH2-EPHB6 axis enhances filopodia formation in hepatocellular carcinoma cells by regulating RHOF.Cell & bioscience · 2026Article
- The RBP2-BECN1-VEGFA axis orchestrates a self-amplifying circuit to drive malignant progression in gastric carcinoma.Frontiers in oncology · 2026Article
- NRF1-mediated innate immune response drives inflammaging.Nature communications · 2025Article
- HIV-associated non-Hodgkin lymphoma tumor-microenvironment axes differ by EBV status across cellular origins.bioRxiv : the preprint server for biology · 2025Article
- Association analysis of intratumoral metabolic heterogeneity assessed by the hottest lesion based onQuantitative imaging in medicine and surgery · 2025Article
- LncRNAs in hypoxic microenvironment; insight in their impact in cancer biology.Functional & integrative genomics · 2025Review
- Inhibition of NFE2L1 Enables the Tumor-Associated Macrophage Polarization and Enhances Anti-PD1 Immunotherapy in Glioma.CNS neuroscience & therapeutics · 2025Article
- ALOX15B-based efferocytosis clusters: prognostic implications and immune cell infiltration in breast cancer.Discover oncology · 2025Article
- Construction and validation of antibody dependent cell phagocytosis related risk model in breast cancer.Scientific reports · 2025Article
- Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate.Aging cell · 2025Review
- The E3-ligase Siah2 activates mitochondrial quality control in neurons to maintain energy metabolism during ischemic brain tolerance.Cell death & disease · 2025Article
- Harnessing Macrophages in Cancer Therapy: from Immune Modulators to Therapeutic Targets.International journal of biological sciences · 2025Review
- Radiotherapy-induced alterations in tumor microenvironment: metabolism and immunity.Frontiers in cell and developmental biology · 2025Review
- hnRNPH1 maintains mitochondrial homeostasis by establishing NRF1/DRP1 retrograde signaling under mitochondrial stress.Cell death and differentiation · 2025Article
- Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment.Biomarker research · 2024Review
- Article
- Combining bulk and scRNA-seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC.Journal of cellular and molecular medicine · 2024Article
3 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
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interactions between tumor cells with their microenvironments, including hypoxia, acidosis and immune cells, lead to the tumor heterogeneity which promotes tumor progression. Here, we show that SIAH2-NRF1 axis remodels tumor microenvironment through regulating tumor mitochondrial function, tumor-associated macrophages (TAMs) polarization and cell death for tumor maintenance and progression. Mechanistically, low mitochondrial gene expression in breast cancers is associated with a poor clinical outcome. The hypoxia-activated E3 ligase SIAH2 spatially downregulates nuclear-encoded mitochondrial gene expression including pyruvate dehydrogenase beta via degrading NRF1 (Nuclear Respiratory Factor 1) through ubiquitination on lysine 230, resulting in enhanced Warburg effect, metabolic reprogramming and pro-tumor immune response. Dampening NRF1 degradation under hypoxia not only impairs the polarization of TAMs, but also promotes tumor cells to become more susceptible to apoptosis in a FADD-dependent fashion, resulting in secondary necrosis due to the impairment of efferocytosis. These data represent that inhibition of NRF1 degradation is a potential therapeutic strategy against cancer.
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