ArticleInternational journal of biological sciences2019
Verteporfin blocks Clusterin which is required for survival of gastric cancer stem cell by modulating HSP90 function.
Article in International journal of biological sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Impact of severe hypoglycemia on the heat shock and related protein response.Scientific reports · 2021Trial
- Therapeutic strategy for cervical gastric-type adenocarcinoma by targeting CLU to relieve CLU-associated stress and sensitize chemotherapy.Precision clinical medicine · 2026Article
- FOXP2 suppresses gastric cancer progression by transcriptionally repressing FBXW2 via WASL degradation.Cell death discovery · 2025Article
- Hotspots and trends in gastric cancer stem cell research: a visualization and bibliometric analysis.Frontiers in oncology · 2025Review
- Review
- Clusterin: a marker and mediator of chemoresistance in colorectal cancer.Cancer metastasis reviews · 2024Review
- The role and function of CLU in cancer biology and therapy.Clinical and experimental medicine · 2023Review
- Repurposed Drugs in Gastric Cancer.Molecules (Basel, Switzerland) · 2022Review
- BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling.Nature communications · 2022Article
- Review
- The origin of gastric cancer stem cells and their effects on gastric cancer: Novel therapeutic targets for gastric cancer.Frontiers in oncology · 2022Review
- Insight into the molecular mechanisms of gastric cancer stem cell in drug resistance of gastric cancer.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- CircSTK40 contributes to recurrent implantation failure via modulating the HSP90/AKT/FOXO1 axis.Molecular therapy. Nucleic acids · 2021Article
- Photosensitizer verteporfin inhibits the growth of YAP- and TAZ-dominant gastric cancer cells by suppressing the anti-apoptotic protein Survivin in a light-independent manner.Oncology letters · 2021Article
- Small Heat Shock Proteins in Cancers: Functions and Therapeutic Potential for Cancer Therapy.International journal of molecular sciences · 2020Review
- Review
- Gastric Cancer Stem Cells: Current Insights into the Immune Microenvironment and Therapeutic Targets.Biomedicines · 2020Review
- The Role of Photoactivated and Non-Photoactivated Verteporfin on Tumor.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer stem cell (GCSC) is implicated in gastric cancer relapse, metastasis and drug resistance. However, the key molecule(s) involved in GCSC survival and the targeting drugs are poorly understood. We discovered increased secreted clusterin (S-Clu) protein expression during the sphere-forming growth of GCSC via mass spectrometry. Overexpression of clusterin was detected in 69/90 (77%) of primary GC tissues and significantly associated with T stage, lymph node metastasis and TNM stage. Depletion of clusterin (Clu, the full-length intracellular clusterin) led to the declustering of GCSC tumorspheres and apoptosis of GCSC. Subsequently, we found clusterin was in complex with heat shock protein 90 beta (HSP90) and involved in regulating the cellular level of HSP90 client proteins. Furthermore, by screening a collection of drugs/inhibitors, we found that verteporfin (VP), a phototherapy drug, blocked clusterin gene expression, decreased the HSP90 client proteins and caused cell death of GCSC. VP treatment is more effective in eradicating GCSCs than in killing GC cells. Both clusterin silencing or VP treatment deterred tumor growth in human GCSC xenografts. These findings collectively suggest that GC patients can promptly benefit from clusterin-targeted therapy as well as VP treatment in combination with or subsequent to conventional chemotherapy for reducing mortality of GC.
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Registered trials
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