ArticlePloS one2015
Blockage of conformational changes of heat shock protein gp96 on cell membrane by a α-helix peptide inhibits HER2 dimerization and signaling in breast cancer.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Chronic ER Stress Triggers Cell-Surface Chaperones as the Therapeutic Targets of CAR Cells in Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Recent Advances in Therapeutic Peptides: Innovations and Applications in Treating Infections and Diseases.ACS omega · 2025Review
- Predictive and Prognostic Values of Glycoprotein 96, Androgen Receptors, and Extranodal Extension in Sentinel Lymph Node-Positive Breast Cancer: An Immunohistochemical Retrospective Study.Journal of clinical medicine · 2024Article
- Discovery of a Therapeutic Agent for Glioblastoma Using a Systems Biology-Based Drug Repositioning Approach.International journal of molecular sciences · 2024Article
- Recent advances in peptide-based therapeutic strategies for breast cancer treatment.Frontiers in pharmacology · 2023Review
- The biology and inhibition of glucose-regulated protein 94/gp96.Medicinal research reviews · 2022Review
- Hypoxia-Induced Intracellular and Extracellular Heat Shock Protein gp96 Increases Paclitaxel-Resistance and Facilitates Immune Evasion in Breast Cancer.Frontiers in oncology · 2021Article
- Molecular Chaperone GRP94/GP96 in Cancers: Oncogenesis and Therapeutic Target.Frontiers in oncology · 2021Review
- Peptides to combat viral infectious diseases.Peptides · 2020Review
- Extracellular gp96 is a crucial mediator for driving immune hyperactivation and liver damage.Scientific reports · 2020Article
- Membrane-Associated Heat Shock Proteins in Oncology: From Basic Research to New Theranostic Targets.Cells · 2020Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell membrane translocation of heat shock protein gp96 from the endoplasmic reticulum has been observed in multiple tumors and is associated with tumor malignancy. However, the cancer-intrinsic function and the related mechanism of cell membrane gp96 as a pro-oncogenic chaperone remain further elucidated. In this study, we found that inhibition of gp96 intramolecular conformational changes by a single α-helix peptide p37 dramatically increased its binding to HER2, whereas decreased HER2 dimerization, phosphorylation and downstream signaling. Targeting cell membrane gp96 promoted HER2 ubiquitination and subsequent lysosomal degradation, which led to decreased cell growth and increased apoptosis, and inhibited tumor growth in vivo. We also demonstrate that gp96 inhibitory peptide p37 synergized with trastuzumab to suppress cell growth and induce apoptosis. Our work demonstrates that blocking gp96 conformational changes directs HER2 for cellular degradation, and represents a new therapeutic strategy for inhibiting HER2 signaling in cancer.
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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.