ArticleCell research2022
EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription.
Article in Cell research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 69 citations in OpenAlex.
- Invas: an inversion-aware method for transcriptome assembly.Nature communications · 2026Article
- Non-canonical function of transferrin receptor-1 promotes breast cancer metastasis by activating HCK‒STAT3‒MMP9 signalling.Clinical and translational medicine · 2026Article
- Nuclear factor IX promotes endometriosis progression through transcriptional activation of tetraspanin-2.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Structural Evolution and Immunomodulatory Versatility of Fungal Immunomodulatory Proteins: Insights into Mechanisms and Bioproduction Strategies.Journal of agricultural and food chemistry · 2026Review
- Phosphorylated-EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis.Oncology letters · 2026Article
- Tetraspanin 13 Enhances Immune Evasion in Breast Cancer by Promoting MHC-I Degradation.Cancer research · 2026Article
- Effects of luteolin on proliferation and apoptosis of breast cancer cells by regulating EGFR/STAT3/AKt pathway.Open life sciences · 2026Article
- Focal adhesion kinase/Src family kinase axis-mediated tyrosine phosphorylation of metabolic enzymes facilitates tumor metastasis.Signal transduction and targeted therapy · 2025Article
- GPR81 nuclear transportation is critical for cancer growth and progression in lung and other solid cancers.World journal of clinical oncology · 2025Article
- Article
- Phosphorylated Toll-like receptor 3 nuclear translocation in cancer cell promotes metastasis and chemoresistance.Signal transduction and targeted therapy · 2025Article
- Cancer stem cells-derived exosomal TSPAN8 enhances non-stem cancer cells stemness and promotes malignant progression in PDAC.Oncogene · 2025Article
- Extracellular vesicles: the "Trojan Horse" within breast cancer host microenvironments.Molecular cancer · 2025Review
- Exosomal Lipids in Cancer Progression and Metastasis.Cancer medicine · 2025Review
- Nerve Growth Factor Signaling Promotes Nuclear Translocation of TRAF4 to Enhance Tumor Stemness and Metastatic Dormancy Via C-Jun-mediated IL-8 Autocrine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RNF31 induces paclitaxel resistance by sustaining ALYREF cytoplasmic-nuclear shuttling in human triple-negative breast cancer.Clinical and translational medicine · 2025Article
- DUSP3 restrains the progression and stemness property of osteosarcoma through regulating EGFR/STAT3/SOX2 axis.International journal of biological sciences · 2025Article
- Palmitoylation in cancer: decoding its roles in signal transduction, tumor immunity, and emerging therapeutic opportunities.Frontiers in immunology · 2025Review
- Nuclear transmembrane protein 199 promotes immune escapes by up-regulating programmed death ligand 1.iScience · 2024Article
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
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17 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
TSPAN family of proteins are generally considered to assemble as multimeric complexes on the plasma membrane. Our previous work uncovered that TSPAN8 can translocate into the nucleus as a membrane-free form, a process that requires TSPAN8 palmitoylation and association with cholesterol to promote its extraction from the plasma membrane and subsequent binding with 14-3-3θ and importin-β. However, what upstream signal(s) regulate(s) the nuclear translocation of TSPAN8, the potential function of TSPAN8 in the nucleus, and the underlying molecular mechanisms all remain unclear. Here, we demonstrate that, epidermal growth factor receptor (EGFR) signaling induces TSPAN8 nuclear translocation by activating the kinase AKT, which in turn directly phosphorylates TSPAN8 at Ser129, an event essential for its binding with 14-3-3θ and importin ß1. In the nucleus, phosphorylated TSPAN8 interacts with STAT3 to enhance its chromatin occupancy and therefore regulates transcription of downstream cancer-promoting genes, such as MYC, BCL2, MMP9, etc. The EGFR-AKT-TSPAN8-STAT3 axis was found to be hyperactivated in multiple human cancers, and associated with aggressive phenotype and dismal prognosis. We further developed a humanized monoclonal antibody hT8
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