ArticleCancer communications (London, England)2022
HSF1 facilitates the multistep process of lymphatic metastasis in bladder cancer via a novel PRMT5-WDR5-dependent transcriptional program.
Article in Cancer communications (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Fibroblast growth factor receptor 3 mutation attenuates response to immune checkpoint blockade in metastatic urothelial carcinoma by driving immunosuppressive microenvironment.Journal for immunotherapy of cancer · 2023Pooled it
- PRMT5 promotes ferroptosis in cisplatin-induced acute kidney injury through WDR5/ACSL4 pathway.Redox biology · 2026Article
- IER5L Facilitates the Progression of Hormone Receptor-Positive Breast Cancer by Inhibiting HSF1 Phosphorylation in Response to Bevacizumab.Cell biochemistry and biophysics · 2026Article
- DIXDC1 Promotes Lymphatic Metastasis and Resistance to Cuproptosis in Bladder Cancer Through Mediating DLAT.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CIITA/PRMT5 promote CD4BMC medicine · 2026Article
- NFYB-lncRNA axis resets the tumor microenvironment to promote HCC aggressive progression by a positive feedback loop.Acta pharmaceutica Sinica. B · 2026Article
- Immunotherapy 3.0: Breakthroughs Steering the Next Generation of Cancer Control.Cancer reports (Hoboken, N.J.) · 2026Review
- SPOCK1 acts as a negative regulator of ferroptosis in non-small cell lung cancer.NPJ precision oncology · 2026Article
- Evaluation of human epidermal growth factor receptor 2 (HER2)-related genes revealed that HER2-antibody-drug conjugate (ADC) drugs confer clinical benefits to Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer patients.Translational andrology and urology · 2026Article
- FomA-Containing Outer Membrane Vesicles of Fusobacterium Nucleatum Facilitate Bladder Cancer Lymphatic Metastasis via IL-6-Dependent M2b Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis.Genes & diseases · 2025Article
- TRIM26 as a dual regulator of ferroptosis and chemoresistance in gastric cancer through HSF1 ubiquitination and exosomal miR-24-3p signaling.Translational oncology · 2025Article
- Patient-derived xenograft models: Current status, challenges, and innovations in cancer research.Genes & diseases · 2025Review
- Silica Nanoparticles Induced Epithelial-Mesenchymal Transition in BEAS-2B Cells via ER Stress and SIRT1/HSF1/HSPs Signaling Pathway.Journal of xenobiotics · 2025Article
- The ETS transcription factor GABPA inhibits bladder cancer aggressiveness by repressing extracellular matrix deposition and mechanotransduction signaling.Cell death & disease · 2025Article
- Heat shock factor 1 promotes proliferation and chemoresistance in diffuse large B-cell lymphoma by enhancing the cell cycle and DNA repair.Cell death & disease · 2025Article
- Methionine Dependency and Restriction in Cancer: Exploring the Pathogenic Function and Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The role of CDK8 gene polymorphisms in bladder cancer susceptibility and prognosis: a study in the Chinese Han population.BMC cancer · 2025Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic options. Emerging evidence shows that heat shock factor 1 (HSF1) drives diversified transcriptome to promote tumor growth and serves as a promising therapeutic target. However, the roles of HSF1 in lymphatic metastasis remain largely unknown. Herein, we aimed to illustrate the clinical roles and mechanisms of HSF1 in the lymphatic metastasis of bladder cancer and explore its therapeutic potential.
methodsWe screened the most relevant gene to lymphatic metastasis among overexpressed heat shock factors (HSFs) and heat shock proteins (HSPs), and analyzed its clinical relevance in three cohorts. Functional in vitro and in vivo assays were performed in HSF1-silenced and -regained models. We also used Co-immunoprecipitation to identify the binding proteins of HSF1 and chromatin immunoprecipitation and dual-luciferase reporter assays to investigate the transcriptional program directed by HSF1. The pharmacological inhibitor of HSF1, KRIBB11, was evaluated in popliteal lymph node metastasis models and patient-derived xenograft models of bladder cancer.
resultsHSF1 expression was positively associated with lymphatic metastasis status, tumor stage, advanced grade, and poor prognosis of bladder cancer. Importantly, HSF1 enhanced the epithelial-mesenchymal transition (EMT) of cancer cells in primary tumor to initiate metastasis, proliferation of cancer cells in lymph nodes, and macrophages infiltration to facilitate multistep lymphatic metastasis. Mechanistically, HSF1 interacted with protein arginine methyltransferase 5 (PRMT5) and jointly induced the monomethylation of histone H3 at arginine 2 (H3R2me1) and symmetric dimethylation of histone H3 at arginine 2 (H3R2me2s). This recruited the WD repeat domain 5 (WDR5)/mixed-lineage leukemia (MLL) complex to increase the trimethylation of histone H3 at lysine 4 (H3K4me3); resulting in upregulation of lymphoid enhancer-binding factor 1 (LEF1), matrix metallopeptidase 9 (MMP9), C-C motif chemokine ligand 20 (CCL20), and E2F transcription factor 2 (E2F2). Application of KRIBB11 significantly inhibited the lymphatic metastasis of bladder cancer with no significant toxicity.
conclusionOur findings reveal a novel transcriptional program directed by the HSF1-PRMT5-WDR5 axis during the multistep process of lymphatic metastasis in bladder cancer. Targeting HSF1 could be a multipotent and promising therapeutic strategy for bladder cancer patients with lymphatic metastasis.
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