ArticleAutophagy2018
HMGB1 represses the anti-cancer activity of sunitinib by governing TP53 autophagic degradation via its nucleus-to-cytoplasm transport.
Article in Autophagy, 2018. 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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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Value of HMGB1 expression for assessing gastric cancer severity: a systematic meta-analysis.The Journal of international medical research · 2021Pooled it
- Regulation of autophagy by the p53 family and the implications for cancer therapies.Discover oncology · 2026Review
- HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025Review
- The inducible role of autophagy in cell death: emerging evidence and future perspectives.Cell communication and signaling : CCS · 2025Review
- PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53.Journal of translational medicine · 2025Article
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- PLAC8 attenuates pulmonary fibrosis and inhibits apoptosis of alveolar epithelial cells via facilitating autophagy.Communications biology · 2025Article
- HMGB1 as an extracellular pro-inflammatory cytokine: Implications for drug-induced organic damage.Cell biology and toxicology · 2024Review
- Multi-center validation of an immune-related lncRNA signature for predicting survival and immune status of patients with renal cell carcinoma: an integrating machine learning-derived study.Journal of cancer research and clinical oncology · 2023Article
- RBM47 restrains renal cell carcinoma progression and chemoresistance through interacting with lncRNA HOXB-AS1.Cell death discovery · 2023Article
- Mechanisms involved in the HMGB1 modulation of tumor multidrug resistance (Review).International journal of molecular medicine · 2023Article
- Regorafenib inhibits EphA2 phosphorylation and leads to liver damage via the ERK/MDM2/p53 axis.Nature communications · 2023Article
- HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma.Molecular biology reports · 2022Article
- Anticancer Therapeutic Strategies Targeting p53 Aggregation.International journal of molecular sciences · 2022Review
- Autophagic degradation of CCN2 (cellular communication network factor 2) causes cardiotoxicity of sunitinib.Autophagy · 2022Article
- The dual role of p62 in ferroptosis of glioblastoma according to p53 status.Cell & bioscience · 2022Article
- Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization.Journal of experimental & clinical cancer research : CR · 2022Article
- The mechanism of HMGB1 secretion and release.Experimental & molecular medicine · 2022Review
- p53 Modulation of Autophagy Signaling in Cancer Therapies: Perspectives Mechanism and Therapeutic Targets.Frontiers in cell and developmental biology · 2022Review
- New Insights into the Link between Melanoma and Thyroid Cancer: Role of Nucleocytoplasmic Trafficking.Cells · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sunitinib, a multikinase inhibitor approved for a number of cancer indications has a low response rate. Identifying mechanisms of resistance could lead to rational combination regimens that could improve clinical outcomes. Here we report that resistance to sunitinib therapy was driven by autophagic degradation of TP53/p53. Deletion of ATG7 or ATG5 suppressed TP53 degradation, as did knockdown of SQSTM1/p62. Mechanistically, the transport of TP53 from the nucleus to the cytoplasm was essential for the sunitinib-induced autophagic degradation of TP53 and did not require TP53 nuclear export signals (NESs). Moreover, TP53 degradation was achieved by the transport of its nuclear binding target, HMGB1, which shifted TP53 from the nucleus to the cytoplasm. The inhibition of HMGB1 sensitized cancer cells to sunitinib. Importantly, sunitinib induced the degradation of all TP53 proteins, except for TP53 proteins with mutations in the interaction domain of TP53 with HMGB1 (amino acids 313 to 352). In conclusion, our data identify an alternative HMGB1-mediated TP53 protein turnover mechanism that participates in the resistance of sunitinib and suggest HMGB1 as a potential therapeutic target for improving clinical outcomes of sunitinib.
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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.