ArticleJournal of experimental & clinical cancer research : CR2020
A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- The research trends and hotspots of claudins in the field of cancer.Cell adhesion & migration · 2025Review
- Weighted overlapping group lasso for integrating prior network knowledge into gene set analysis.BMC bioinformatics · 2025Article
- SENP1: A perspective from immune cells to disease (Review).Oncology reports · 2025Review
- HIF-1α Promotes the Confined Migration of Gastric Cancer Cells by Modulating Phosphatidylcholine Metabolism.Journal of cellular and molecular medicine · 2025Article
- Sentrin/SUMO-specific protease 1 contributes to drug resistance in melanoma by mediating the deSUMOylation of Yes-associated protein.Postepy dermatologii i alergologii · 2025Article
- Knockdown of Claudin-8 (CLDN8) Indicates a Link Between Breast Cancer Cell Sensitivity to Chemotherapeutics and Reveals a Potential Use of CLDN8 as a Molecular Diagnostic and Target for Therapy.International journal of molecular sciences · 2025Article
- Suppressing SENP1 inhibits esophageal squamous carcinoma cell growth via SIRT6 SUMOylation.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
- CLDN6 induces chemoresistance through protective autophagy in breast cancer.International journal of biological sciences · 2025Article
- Tight junctional protein family, Claudins in cancer and cancer metastasis.Frontiers in oncology · 2025Review
- CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation.Cellular & molecular biology letters · 2024Article
- SENP1 reduces oxidative stress and apoptosis in renal ischaemia-reperfusion injury by deSUMOylation of HIF-1α.Journal of cellular and molecular medicine · 2024Article
- SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins.Open medicine (Warsaw, Poland) · 2024Article
- Emerging role of SENP1 in tumorigenesis and cancer therapy.Frontiers in pharmacology · 2024Review
- Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.Theranostics · 2024Review
- Anti-apoptotic capacity of MALAT1 on hippocampal neurons correlates with CASP3 DNA methylation in a mouse model of autism.Metabolic brain disease · 2023Article
- Binding of YY1/CREB to an Enhancer Region Triggers Claudin 6 Expression inInternational journal of molecular sciences · 2023Article
- The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications.Experimental hematology & oncology · 2023Review
- HIF-1α contributes to metastasis in choriocarcinoma by regulating DEC1 expression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- CLDN6 inhibits breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy.Journal of experimental & clinical cancer research : CR · 2023Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe have previously described CLDN6 as a tumor suppressor gene in breast cancer. Here, a new finding is that CLDN6 was upregulated under hypoxia, a commonly recognized factor that promotes tumor metastasis. In this study, we aim to explain this confusing finding and delineate the role of CLDN6 in the breast cancer metastasis induced by hypoxia.
methodsRNAi and ChIP assays were used to confirm that CLDN6 is transcriptional regulated by HIF-1α. mRNA seq and KEGG analysis were performed to define the downstream pathways of CLDN6. The roles of the CLDN6/SENP1/HIF-1α signaling on tumor metastasis were evaluated by function experiments and clinical samples. Finally, the possible transcription factor of SENP1 was suspected and then validated by ChIP assay.
resultsWe demonstrated a previously unrecognized negative feedback loop exists between CLDN6 and HIF-1α. CLDN6 was transcriptionally up-regulated by HIF-1α under hypoxia. On the other hand, in cytoplasm CLDN6 combines and retains β-catenin, a transcription factor of SENP1, causing β-catenin degradation and preventing its nuclear translocation. This process reduced SENP1 expression and prevented the deSUMOylation of HIF-1α, ultimately leading to HIF-1α degradation and breast cancer metastasis suppression.
conclusionsOur data provide a molecular mechanistic insight indicating that CLDN6 loss may lead to elevated HIF-1α-driven breast cancer metastasis in a SUMOylation-dependent manner.
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