ArticleOncogene2016
Deacetylation of HSPA5 by HDAC6 leads to GP78-mediated HSPA5 ubiquitination at K447 and suppresses metastasis of breast cancer.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers, 3 of them syntheses that pooled it.
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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
49 citing papers in PubMed, 3 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection.Current oncology (Toronto, Ont.) · 2022Pooled it
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- Computational Identification of Novel Stage-Specific Biomarkers in Colorectal Cancer Progression.PloS one · 2016Pooled it
- Death-associated protein kinase 2 (DAPK2) propagates endoplasmic reticulum stress in macrophages to worsen sepsis through HSPA5-IRE1α axis.Molecular biomedicine · 2026Article
- HSPA5 overexpression predicts poor prognosis and drives radioresistance and metastasis in nasopharyngeal carcinoma.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Autophagy selectively clears ER in TNF-α-induced muscle atrophy.Autophagy reports · 2026Article
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- Article
- Acetylation: a new target for protein degradation in cancer.Trends in cancer · 2025Review
- Diagnostic, prognostic, and therapeutic potential of exosomal microRNAs in renal cancer.Pharmacological reports : PR · 2024Review
- Regulator of Ribosome Synthesis 1 (RRS1) Stabilizes GRP78 and Promotes Breast Cancer Progression.Molecules (Basel, Switzerland) · 2024Article
- Pentapeptide PYRAE triggers ER stress-mediated apoptosis of breast cancer cells in mice by targeting RHBDF1-BiP interaction.Acta pharmacologica Sinica · 2024Article
- Molecular mechanism and therapeutic potential of HDAC9 in intervertebral disc degeneration.Cellular & molecular biology letters · 2023Article
- EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer.Scientific reports · 2023Article
- Therapeutic hyperthermia regulates complement C3 activation and suppresses tumor development through HSPA5/NFκB/CD55 pathway in nasopharyngeal carcinoma.Clinical and experimental immunology · 2023Article
- Discovery of an OTUD3 inhibitor for the treatment of non-small cell lung cancer.Cell death & disease · 2023Article
- iASPP suppression mediates terminal UPR and improves BRAF-inhibitor sensitivity of colon cancers.Cell death and differentiation · 2023Article
- A human pan-cancer system analysis of heat shock protein family A member 5.American journal of cancer research · 2023Article
- Characterization of Small Genetic Variants in Breast Cancer Cell Line Under Tamoxifen Therapy.Galen medical journal · 2023Article
- CDK7/GRP78 signaling axis contributes to tumor growth and metastasis in osteosarcoma.Oncogene · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Heat-shock protein 5 (HSPA5) is a marker for poor prognosis in breast cancer patients and has an important role in cancer progression, including promoting drug resistance and metastasis. In this study, we identify that the specific lysine residue 447 (K447) of HSPA5 could be modified with polyubiquitin for subsequent degradation through the ubiquitin proteasomal system, leading to the suppression of cell migration and invasion of breast cancer. We further found that GP78, an E3 ubiquitin ligase, interacted with the C-terminal region of HSPA5 and mediated HSPA5 ubiquitination and degradation. Knock down of GP78 significantly increased the expression of HSPA5 and enhanced migration/invasive ability of breast cancer cells. Knock down of histone deacetylase-6 (HDAC6) increased the acetylation of HSPA5 at lysine residues 353 (K353) and reduced GP78-mediated ubiquitination of HSPA5 at K447 and then increased cell migration/invasion. In addition, we demonstrate that E3 ubiquitin ligase GP78 preferentially binds to deacetylated HSPA5. Notably, the expression levels of GP78 inversely correlated with HSPA5 levels in breast cancer patients. Patients with low GP78 expression significantly correlated with invasiveness of breast cancer, advanced tumor stages and poor clinical outcome. Taken together, our results provide new mechanistic insights into the understanding that deacetylation of HSPA5 by HDAC6 facilitates GP78-mediated HSPA5 ubiquitination and suggest that post-translational regulation of HSPA5 protein is critical for HSPA5-mediated metastatic properties of breast cancer.
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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.