ArticleCell reports2015
HUWE1 ubiquitylates and degrades the RAC activator TIAM1 promoting cell-cell adhesion disassembly, migration, and invasion.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer.Cell death & disease · 2026Article
- The multifaceted role of E3 ubiquitin ligases in cancer metastasis: mechanisms, targets, and therapeutic implications.Essays in biochemistry · 2025Review
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- Targeting Tiam1 Enhances Hippocampal-Dependent Learning and Memory in the Adult Brain and Promotes NMDA Receptor-Mediated Synaptic Plasticity and Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Multi-Omics Characterization of E3 Regulatory Patterns in Different Cancer Types.International journal of molecular sciences · 2024Article
- JMJD5 inhibits lung cancer progression by facilitating EGFR proteasomal degradation.Cell death & disease · 2023Article
- Spatiotemporal regulation of Rho GTPase signaling during endothelial barrier remodeling.Current opinion in physiology · 2023Review
- Biological insights in non-small cell lung cancer.Cancer biology & medicine · 2023Review
- Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells.iScience · 2022Article
- The giant E3 ligase HUWE1 is linked to tumorigenesis, spermatogenesis, intellectual disability, and inflammatory diseases.Frontiers in cellular and infection microbiology · 2022Review
- Regulation of tamoxifen sensitivity by the PLAC8/MAPK pathway axis is antagonized by curcumin-induced protein stability change.Journal of molecular medicine (Berlin, Germany) · 2021Article
- The RAC1 activator Tiam1 regulates centriole duplication through controlling PLK4 levels.Journal of cell science · 2021Article
- Benefits of Zebrafish Xenograft Models in Cancer Research.Frontiers in cell and developmental biology · 2021Review
- The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma.Oncogene · 2020Article
- The structure and regulation of the E3 ubiquitin ligase HUWE1 and its biological functions in cancer.Investigational new drugs · 2020Review
- Mechanical Cues Affect Migration and Invasion of Cells From Three Different Directions.Frontiers in cell and developmental biology · 2020Review
- ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis.Journal of experimental & clinical cancer research : CR · 2019Article
- A complex containing theThe Journal of biological chemistry · 2019Article
- Spatial Rho regulation: Molecular mechanisms controlling the GAP protein DLC3.Small GTPases · 2019Article
- The Fibroblast TIAM2 Promotes Lung Cancer Cell Invasion and Metastasis.Journal of Cancer · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The E3 ubiquitin ligase HUWE1, deregulated in carcinoma, has been implicated in tumor formation. Here, we uncover a role for HUWE1 in cell migration and invasion through degrading the RAC activator TIAM1, implying an additional function in malignant progression. In MDCKII cells in response to HGF, HUWE1 catalyzes TIAM1 ubiquitylation and degradation predominantly at cell-cell adhesions, facilitating junction disassembly, migration, and invasion. Depleting HUWE1 or mutating the TIAM1 ubiquitylation site prevents TIAM1 degradation, antagonizing scattering, and invasion. Moreover, simultaneous depletion of TIAM1 restores migration and invasion in HUWE1-depleted cells. Significantly, we show that HUWE1 stimulates human lung cancer cell invasion through regulating TIAM1 stability. Finally, we demonstrate that HUWE1 and TIAM1 protein levels are inversely correlated in human lung carcinomas. Thus, we elucidate a critical role for HUWE1 in regulating epithelial cell-cell adhesion and provide additional evidence that ubiquitylation contributes to spatiotemporal control of RAC.
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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.