ArticleEBioMedicine2018
Proapoptotic Cyclic Peptide BC71 Targets Cell-Surface GRP78 and Functions as an Anticancer Therapeutic in Mice.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- GRP78 dysregulation: A proposed molecular mechanism linking the tumor microenvironment to sepsis susceptibility in patients with cancer (Review).International journal of molecular medicine · 2026Review
- Inhibition of PERK signaling suppresses tumor progression and blocks GP73-GRP78-dependent stromal activation in hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2026Article
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Crystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling.Nature communications · 2025Article
- GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.Frontiers in oncology · 2024Review
- Advances in research of biological functions of Isthmin-1.Journal of cell communication and signaling · 2023Review
- A computational peptide model induces cancer cells' apoptosis by docking Kringle 5 to GRP78.BMC molecular and cell biology · 2023Article
- Article
- New progresses on cell surface protein HSPA5/BiP/GRP78 in cancers and COVID-19.Frontiers in immunology · 2023Review
- Isthmin-A Multifaceted Protein Family.Cells · 2022Review
- Physiological Roles of the Autoantibodies to the 78-Kilodalton Glucose-Regulated Protein (GRP78) in Cancer and Autoimmune Diseases.Biomedicines · 2022Review
- Review
- Identification of Isthmin1 in the small annual fish, Nothobranchius guentheri, as a novel biomarker of aging and its potential rejuvenation activity.Biogerontology · 2022Article
- A brief overview about the adipokine: Isthmin-1.Frontiers in cardiovascular medicine · 2022Review
- HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy.Cells · 2021Review
- Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRBiomedicines · 2021Review
- Proteins Marking the Sequence of Genotoxic Signaling from Irradiated Mesenchymal Stromal Cells to CD34+ Cells.International journal of molecular sciences · 2021Article
- Evaluation and characterization of HSPA5 (GRP78) expression profiles in normal individuals and cancer patients with COVID-19.International journal of biological sciences · 2021Article
- Tumor-Secreted GRP78 Promotes the Establishment of a Pre-metastatic Niche in the Liver Microenvironment.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucose regulated protein 78 kDa (GRP78) is a recently emerged target for cancer therapy and a biomarker for cancer prognosis. Overexpression of GRP78 is observed in many types of cancers, with the cell-surface GRP78 being preferentially present in cancer cells and cancer blood vessel endothelial cells. Isthmin (ISM) is a secreted high-affinity proapoptotic protein ligand of cell-surface GRP78 that suppresses angiogenesis and tumor growth in mice. The C-terminal AMOP (adhesion-associated domain in MUC4 and other proteins) domain of ISM is critical in mediating its interaction with human umbilical vein endothelial cells (HUVECs). In this work, we report novel cyclic peptides harboring the RKD motif in the ISM AMOP domain that function as proapoptotic ligands of cell-surface GRP78. The most potent peptide, BC71, binds to GRP78 and converge to tumor in mice. Intravenous administration of BC71 suppressed xenograft tumor growth in mice as a single agent, with significant reduction in tumor angiogenesis and upsurge in apoptosis. Fluorescent-labeled BC71 accumulates in tumor in mice by targeting cell-surface GRP78. We show that BC71 triggers apoptosis via cell-surface GRP78 and activates caspase-8 and p53 signaling pathways in HUVECs. Using amide hydrogen-deuterium exchange mass spectrometry (HDXMS), we identified that BC71 preferentially binds to ATP-bound GRP78 via amino acid residues 244-257 of GRP78. Hence, BC71 serves as a valuable prototype for further development of peptidomimetic anticancer drugs targeting cell-surface GRP78 as well as PET imaging agents for cancer prognosis.
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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.