ArticleJournal of experimental & clinical cancer research : CR2019
Hypoxia-induced Slug SUMOylation enhances lung cancer metastasis.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- MiR-31 suppresses lung adenocarcinoma cell proliferation through CDK1 and E2F2-mediated cell cycle arrest.Discover oncology · 2026Article
- SENP1: A perspective from immune cells to disease (Review).Oncology reports · 2025Review
- The role of SUMOylation in epithelial-mesenchymal transition.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Development and validation of a hypoxia-immune-based microenvironment gene signature for predicting survival in non-small cell lung cancer.Discover oncology · 2025Article
- The Dynamic Regulation of Daxx-Mediated Transcriptional Inhibition by SUMO and PML NBs.International journal of molecular sciences · 2025Review
- Cancer metastasis: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2025Review
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
- Hypoxia Affects Mitochondrial Stress and Facilitates Tumor Metastasis of Colorectal Cancer Through Slug SUMOylation.Current molecular medicine · 2025Article
- Post-translational modifications of protein and lung cancer.Frontiers in oncology · 2025Review
- The Research Progress of Metformin Regulation of Metabolic Reprogramming in Malignant Tumors.Pharmaceutical research · 2024Review
- Targeted inhibition of SUMOylation: treatment of tumors.Human cell · 2024Review
- Mapping the influence of hydrocarbons mixture on molecular mechanisms, involved in breast and lung neoplasms: in silico toxicogenomic data-mining.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2024Article
- HIF2A mediates lineage transition to aggressive phenotype of cancer-associated fibroblasts in lung cancer brain metastasis.Oncoimmunology · 2024Article
- Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.Theranostics · 2024Review
- Dysregulated gene expression of SUMO machinery components induces the resistance to anti-PD-1 immunotherapy in lung cancer by upregulating the death of peripheral blood lymphocytes.Frontiers in immunology · 2024Article
- The emerging roles of SUMOylation in pulmonary diseases.Molecular medicine (Cambridge, Mass.) · 2023Review
- The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications.Experimental hematology & oncology · 2023Review
- TRIB3 promotes pulmonary fibrosis through inhibiting SLUG degradation by physically interacting with MDM2.Acta pharmaceutica Sinica. B · 2023Article
- Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases.International journal of molecular sciences · 2022Review
- Epithelial-mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities.MedComm · 2022Review
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundThe Slug-E-cadherin axis plays a critical role in non-small-cell lung cancers (NSCLCs) where aberrant upregulation of Slug promotes cancer metastasis. Now, the post-translational modifications of Slug and their regulation mechanisms still remain unclear in lung cancer. Hence, exploring the protein linkage map of Slug is of great interest for investigating the scenario of how Slug protein is regulated in lung cancer metastasis.
methodsThe Slug associated proteins, Ubc9 and SUMO-1, were identified using yeast two-hybrid screening; and in vitro SUMOylation assays combined with immunoprecipitation and immunoblotting were performed to explore the detail events and regulations of Slug SUMOylation. The functional effects of SUMOylation on Slug proteins were examined by EMSA, reporter assay, ChIP assay, RT-PCR, migration and invasion assays in vitro, tail vein metastatic analysis in vivo, and also evaluated the association with clinical outcome of NSCLC patients.
resultsSlug protein could interact with Ubc9 and SUMO-1 and be SUMOylated in cells. Amino acids 130-212 and 33-129 of Slug are responsible for its binding to Ubc9 and protein inhibitor of activated STAT (PIAS)y, respectively. SUMOylation could enhance the transcriptional repression activity of Slug via recruiting more HDAC1, resulting in reduced expression of downstream Slug target genes and enhanced lung cancer metastasis. In addition, hypoxia could increase Slug SUMOylation through attenuating the interactions of Slug with SENP1 and SENP2. Finally, high expression Slug and Ubc9 levels were associated with poor overall survival among NSCLC patients.
conclusionsUbc9/PIASy-mediated Slug SUMOylation and subsequent HDAC1 recruitment may play a crucial role in hypoxia-induced lung cancer progression, and these processes may serve as therapeutic targets for NSCLC.
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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.