ArticleSignal transduction and targeted therapy2022
Targeting HECTD3-IKKα axis inhibits inflammation-related metastasis.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Suspected Donor-Site Implantation of Floor of Mouth Squamous Cell Carcinoma After Free Flap Reconstruction: A Case Report.The American journal of case reports · 2026Article
- Chiral Titanium Dioxide Nanoparticles Induce Breast Cancer Lung Metastasis.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Macrophage USP9X attenuates colitis by restricting oncostatin M production via K27-linked deubiquitination of STAT1.Cellular & molecular immunology · 2026Article
- The vascular niche: an orchestrator of the spatiotemporal dynamics of distant metastasis.Acta pharmacologica Sinica · 2026Review
- The roles of IKKα in normal physiology and cancer.Cell communication and signaling : CCS · 2026Review
- HECT ubiquitin ligases as regulators of inflammatory signalling.Cell death and differentiation · 2026Review
- Molecular mechanisms of PCSK9 in cardiology: therapeutic implications and clinical impacts on the cardiorenal axis.Molecular and cellular biochemistry · 2026Review
- Article
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- Circulating Tumor Microenvironment in Metastasis.Cancer research · 2025Review
- Delivery of miR-26a-5p by Subcutaneous Adipose Tissue-Derived Extracellular Vesicles Alleviates Acute Lung Injury in Mice Through CHUK/NF-κB Pathway.International journal of nanomedicine · 2025Article
- Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells.Cell death discovery · 2024Article
- Epigenetic Modifiers in Cancer Metastasis.Biomolecules · 2024Review
- Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance.Cancer metastasis reviews · 2024Review
- SUMOylation-Driven mRNA Circularization Enhances Translation and Promotes Lymphatic Metastasis of Bladder Cancer.Cancer research · 2024Article
- HECTD3 inhibits NLRP3 inflammasome assembly and activation by blocking NLRP3-NEK7 interaction.Cell death & disease · 2024Article
- CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis.Biomaterials research · 2024Article
- Macrophage polarization in spinal cord injury repair and the possible role of microRNAs: A review.Heliyon · 2023Review
- Stromal cells in the tumor microenvironment: accomplices of tumor progression?Cell death & disease · 2023Review
- Protective Effect and Mechanism of Melatonin on Cisplatin-Induced Ovarian Damage in Mice.Journal of clinical medicine · 2022Article
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Authors and funding
25 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis is the leading cause of cancer-related death. The interactions between circulating tumor cells and endothelial adhesion molecules in distant organs is a key step during extravasation in hematogenous metastasis. Surgery is a common intervention for most primary solid tumors. However, surgical trauma-related systemic inflammation facilitates distant tumor metastasis by increasing the spread and adhesion of tumor cells to vascular endothelial cells (ECs). Currently, there are no effective interventions to prevent distant metastasis. Here, we show that HECTD3 deficiency in ECs significantly reduces tumor metastasis in multiple mouse models. HECTD3 depletion downregulates expression of adhesion molecules, such as VCAM-1, ICAM-1 and E-selectin, in mouse primary ECs and HUVECs stimulated by inflammatory factors and inhibits adhesion of tumor cells to ECs both in vitro and in vivo. We demonstrate that HECTD3 promotes stabilization, nuclear localization and kinase activity of IKKα by ubiquitinating IKKα with K27- and K63-linked polyubiquitin chains at K296, increasing phosphorylation of histone H3 to promote NF-κB target gene transcription. Knockout of HECTD3 in endothelium significantly inhibits tumor cells lung colonization, while conditional knockin promotes that. IKKα kinase inhibitors prevented LPS-induced pulmonary metastasis. These findings reveal the promotional role of the HECTD3-IKKα axis in tumor hematogenous metastasis and provide a potential strategy for tumor metastasis prevention.
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