ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
Extracellular HSP70-peptide complexes promote the proliferation of hepatocellular carcinoma cells via TLR2/4/JNK1/2MAPK pathway.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 31 citations in OpenAlex.
- The Role of the Gut-Biliary-Liver Axis in Primary Hepatobiliary Liver Cancers: From Molecular Insights to Clinical Applications.Journal of personalized medicine · 2025Review
- Mechanism of ozone alleviation of malignant ascites in hepatocellular carcinoma through the inhibition of neutrophil extracellular traps.PNAS nexus · 2023Article
- The Role of TLR4 in the Immunotherapy of Hepatocellular Carcinoma: Can We Teach an Old Dog New Tricks?Cancers · 2023Review
- Chronic Inflammatory and Immune Microenvironment Promote Hepatocellular Carcinoma Evolution.Journal of inflammation research · 2023Review
- Design and optimisation of a small-molecule TLR2/4 antagonist for anti-tumour therapy.RSC medicinal chemistry · 2021Article
- Review
- Are Pattern Recognition Receptors Associated with Hepatocellular Carcinoma?The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2021Article
- Long Noncoding RNA NONHSAT079852.2 Contributes to GBM Recurrence by Functioning as a ceRNA for has-mir-10401-3p to Facilitate HSPA1A Upregulation.Frontiers in oncology · 2021Article
- HSP70-Homolog DnaK ofInternational journal of molecular sciences · 2020Article
- Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma.British journal of pharmacology · 2020Article
- Prognostic impact of toll-like receptors 2 and 4 expression on monocytes in Egyptian patients with hepatocellular carcinoma.Immunologic research · 2019Article
- Role of MicroRNAs Induced by Chinese Herbal Medicines Against Hepatocellular Carcinoma: A Brief Review.Integrative cancer therapies · 2018Review
- Topical heat shock protein 70 prevents imiquimod-induced psoriasis-like inflammation in mice.Cell stress & chaperones · 2018Article
- Prognostic role of Toll-like receptors in cancer: a meta-analysis.Therapeutics and clinical risk management · 2018Article
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Authors and funding
6 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Heat shock protein 70 (HSP70) and HSP70-peptide complexes (HSP70-PCs) have been implicated in the pathogenesis of multiple tumors in humans and have been experimentally shown to increase the proliferation of cell lines derived from hepatocellular carcinoma. The goal of this study was to elucidate the molecular mechanisms through which extracellular HSP70/HSP70-PCs stimulate the proliferation of hepatocellular carcinoma (HCC). The molecular mechanisms of HSP70/HSP70-PC action were studied in the human hepatocellular carcinoma cell lines HepG2 and Huh-7, as well as tumor tissue collected from patients with HCC (n = 95). We found that HSP70/HSP70-PCs can stimulate the proliferation of HepG2 cells and that this effect is blocked by knocking down TLR2 and TLR4 expression by RNA interference. A physical interaction between HSP70/HSP70-PCs and TLR2/4 was established using co-immunoprecipitation and pull-down assays. Pharmacological inhibition of different branches of the MAPK intracellular signaling pathway indicated that the extracellular HSP70/HSP70-PC effect was mediated by the JNK1/2 signaling pathway within the cell. We also studied TLR2 and TLR expression at the protein and messenger RNA (mRNA) level in tumor and non-tumor tissue in patients with HCC (n = 95), finding that TLR2 and 4 are increased in HCC tumor tissue and that the expression of TLR2 correlates with clinicopathologic features of HCC. Our data conclusively demonstrates that extracellular HSP70/HSP70-PCs can promote the proliferation of HCC cells through activation of TLR2 and TLR4 and subsequent activation of the intracellular JNK1/2/MAPK signaling pathway.
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