ArticleNeoplasia (New York, N.Y.)2019
The COOH-Terminal Proline-Rich Region of GRP78 Is a Key Regulator of Its Cell Surface Expression and Viability of Tamoxifen-Resistant Breast Cancer Cells.
Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Role of STAT3 signaling pathway in breast cancer.Cell communication and signaling : CCS · 2020Pooled it
- Chondroitin sulfate shapes the unfolded protein response in osteosarcoma to sustain cancer cell survival during ER stress.Cell death & disease · 2026Article
- Sanguinarine and Doxorubicin Inhibit Heat Shock Protein HSPA5 and Trigger ER Stress in Breast Cancer.Cell biochemistry and biophysics · 2026Article
- Targeting cell surface GRP78-CD44v interaction suppresses cell migration in triple-negative breast cancer cells.Scientific reports · 2025Article
- Article
- The potential role of targeting the leptin receptor as a treatment for breast cancer in the context of hyperleptinemia: a literature review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma.medRxiv : the preprint server for health sciences · 2024Article
- CAR-based immunotherapy for breast cancer: peculiarities, ongoing investigations, and future strategies.Frontiers in immunology · 2024Review
- Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.Frontiers in oncology · 2024Review
- The Effect and Mechanism of POSTN and Its Alternative Splicing on the Apoptosis of Myocardial Cells in Acute Myocardial Infarction: A Study in Vitro.Cell biochemistry and biophysics · 2023Article
- Cell surface GRP78: a potential mechanism of therapeutic resistant tumors.Cancer cell international · 2023Review
- Mechanisms of drug resistance in breast cancer liver metastases: Dilemmas and opportunities.Molecular therapy oncolytics · 2023Review
- Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence.Cancer metastasis reviews · 2023Review
- The therapeutic mavericks: Potent immunomodulating chaperones capable of treating human diseases.Journal of cellular and molecular medicine · 2023Review
- Hydra-Elastin-like Polypeptides Increase Rapamycin Potency When Targeting Cell Surface GRP78.Biomacromolecules · 2022Article
- Review
- Peroxidase from foxtail millet bran exerts anti-colorectal cancer activityActa pharmaceutica Sinica. B · 2022Article
- HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy.Cells · 2021Review
- Suppression of ER-stress induction of GRP78 as an anti-neoplastic mechanism of the cardiac glycoside Lanatoside C in pancreatic cancer: Lanatoside C suppresses GRP78 stress induction.Neoplasia (New York, N.Y.) · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Translocation of 78-kDa glucose-regulated protein (GRP78) from endoplasmic reticulum (ER) to plasma membrane represents a paradigm shift beyond its traditional function as an ER chaperone protein. Cell surface GRP78 (csGRP78) exerts novel signaling functions, and mechanisms underlying its cell surface expression are just emerging. Acquired tamoxifen resistance of breast cancer cells is accompanied with elevated level of csGRP78. Therefore, the tamoxifen-resistant MCF7 breast cancer cells (MCF7-LR) represents a clinically relevant model to study mechanisms of csGRP78 expression. We discovered that a proline-rich region (PRR) containing three consecutive prolines close to the COOH-terminus of GRP78 is important for its ability to form a complex with the partner protein, CD44v, as demonstrated by in vitro glutathione S-transferase pull-down assay. Proline to alanine mutations at the PRR compromised GRP78 expression level on the cell surface as evidenced by purification of biotinylated cell surface proteins. Reconstitution of MCF7-LR cells with the PRR mutant after knockdown of endogenous GRP78 diminished the capacity of GRP78 to stimulate STAT3 activation. The enforced expression of a short peptide bearing the PRR region of GRP78 led to reduction of CD44v and Cyclin D1 protein levels as well as cell viability, accompanied with increase in apoptotic signaling including cleaved Caspase-3 and PARP. These findings suggest that the COOH-terminal PRR of GRP78 is critical for its interaction with CD44v as well as its cell surface expression, and enforced expression of the short peptide bearing the PRR region may provide a new approach to lower the viability of tamoxifen-resistant breast cancer cells.
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