ArticleAutophagy2018
HSPA5 negatively regulates lysosomal activity through ubiquitination of MUL1 in head and neck cancer.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review.Molecular medicine (Cambridge, Mass.) · 2023Pooled it
- Identification and validation of an autophagy-related signature for predicting survival in lower-grade glioma.Bioengineered · 2021Trial
- RNF5 promotes acute lung injury through HSPA5 ER-to-cytosol translocation and resultant PERK activation.Cell death and differentiation · 2026Article
- Death-associated protein kinase 2 (DAPK2) propagates endoplasmic reticulum stress in macrophages to worsen sepsis through HSPA5-IRE1α axis.Molecular biomedicine · 2026Article
- MUL1 suppresses cervical cancer progression by targeting FUNDC1 for ubiquitination and inhibiting DRP1-dependent mitophagy.Journal of molecular histology · 2026Article
- Ubiquitination degradation of GATA4 by CUL4B promotes ovarian cancer metastasis by inducing lysosomal acidification.Genome biology · 2026Article
- Cardiomyocyte-derived USP20 mitigates myocardial ischemia/reperfusion injury through deubiquitinating GRP78.Theranostics · 2026Article
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- Article
- Trim7 aggravates ischemic stroke-associated ferroptosis by promoting ubiquitin-mediated degradation of HSPA5.Cell & bioscience · 2025Article
- The influence of ferroptosis-associated gene HSPA5 on the prognosis and immune evasion of lung adenocarcinoma.Discover oncology · 2025Article
- Liquid Plasma Induces Necroptosis Without Inflammatory Responses in Head and Neck Cancer Cells.World journal of oncology · 2025Article
- Functionally deficient UBOX5 variants and primary angle-closure glaucoma.Nature communications · 2025Article
- TBK1 is a signaling hub in coordinating stress-adaptive mechanisms in head and neck cancer progression.Autophagy · 2025Article
- AKR1C3 enhances radioresistance in esophageal adenocarcinoma via inhibiting ferroptosis through suppressing TRIM21-mediated ubiquitination of HSPA5.Cell death & disease · 2025Article
- The CRISPR-Cas revolution in head and neck cancer: a new era of targeted therapy.Functional & integrative genomics · 2025Review
- Predictive Value and Immunological Role of the HSPA5 Gene in Cervical Cancer.Biochemical genetics · 2025Article
- Article
- Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.Signal transduction and targeted therapy · 2024Review
- Dysregulation of Autophagy Occurs During Congenital Cataract Development in βA3ΔG91 Mice.Investigative ophthalmology & visual science · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HSPA5/GRP78/BiP plays an important role in cell survival or tumor progression. For these reasons, HSPA5 is an emerging therapeutic target in cancer development. Here we report that HSPA5 contributes to head and neck cancer (HNC) survival via maintenance of lysosomal activity; however, a nonthermal plasma (NTP, considered as a next-generation cancer therapy)-treated solution (NTS) inhibits HNC progression through HSPA5-dependent alteration of lysosomal activity. HSPA5 prevents NTS-induced lysosome inhibition through lysosomal-related proteins or regulation of gene expression. However, NTS-induced MUL1/MULAN/GIDE/MAPL (mitochondrial ubiquitin ligase activator of NFKB 1) leads to downregulation of HSPA5 via K48-linked ubiquitination at the lysine 446 (K446) residue. MUL1 knockdown hinders NTS-induced lysosome inhibition or cytotoxicity through the reduction of HSPA5 ubiquitination in HNC cells. While MUL1 was suppressed, HSPA5 was overexpressed in tissues of HNC patients. NTS strongly inhibited HNC progression via alterations of expression of MUL1 and HSPA5, in vivo in a xenograft model. However, NTS did not induce inhibition of tumor progression or HSPA5 reduction in MUL1 knockout (KO) HNC cells which were generated by CRISPR/Cas9 system. The data provide compelling evidence to support the idea that the regulation of the MUL1-HSPA5 axis can be a novel strategy for the treatment of HNC.
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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.