ArticlePloS one2013
Clusterin protects hepatocellular carcinoma cells from endoplasmic reticulum stress induced apoptosis through GRP78.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 72 citations in OpenAlex.
- Article
- Clusterin can mediate apoptosis-induced molecular mechanisms in immune thrombocytopenia.Blood vessels, thrombosis & hemostasis · 2024Article
- Early monitoring values of oncogenic signalling molecules for hepatocellular carcinoma.World journal of gastrointestinal oncology · 2024Article
- CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival.Autophagy · 2024Article
- The role and function of CLU in cancer biology and therapy.Clinical and experimental medicine · 2023Review
- The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.International journal of molecular sciences · 2023Review
- The clusterin connectome: Emerging players in chondrocyte biology and putative exploratory biomarkers of osteoarthritis.Frontiers in immunology · 2023Article
- The Influence of Clusterin Glycosylation Variability on Selected Pathophysiological Processes in the Human Body.Oxidative medicine and cellular longevity · 2022Review
- Comprehensive Identification of Potential Crucial Genes and miRNA-mRNA Regulatory Networks in Papillary Thyroid Cancer.BioMed research international · 2021Article
- Clusterin Protects Lipotoxicity-Induced Apoptosis via Upregulation of Autophagy in Insulin-Secreting Cells.Endocrinology and metabolism (Seoul, Korea) · 2020Article
- Increased expression and retention of the secretory chaperone proSAAS following cell stress.Cell stress & chaperones · 2020Article
- Aspirin inhibits hepatocellular carcinoma cell proliferation in vitro and in vivo via inducing cell cycle arrest and apoptosis.Oncology reports · 2020Article
- Tracking acute phase protein response during acute and chronicLaboratory animal research · 2019Article
- The role of Clusterin in cancer metastasis.Cancer management and research · 2019Article
- Clusterin increases mitochondrial respiratory chain complex I activity and protects against hexavalent chromium-induced cytotoxicity in L-02 hepatocytes.Toxicology research · 2019Article
- Clusterin in Alzheimer's Disease: Mechanisms, Genetics, and Lessons From Other Pathologies.Frontiers in neuroscience · 2019Review
- Reduced glutathione alleviates tunicamycin-induced endoplasmic reticulum stress in mouse preimplantation embryos.The Journal of reproduction and development · 2018Article
- Clusterin promotes growth and invasion of clear cell renal carcinoma cell by upregulation of S100A4 expression.Cancer biomarkers : section A of Disease markers · 2018Article
- GP73 level determines chemotherapeutic resistance in human hepatocellular carcinoma cells.Journal of Cancer · 2018Article
- Secretory Clusterin Mediates Oxaliplatin Resistance via the Gadd45a/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma.Journal of Cancer · 2018Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clusterin (CLU) is a stress-activated chaperone, which plays an important role in cancer development and progression through promoting cell survival. However, the exact mechanism of how CLU exerts its cell protective role under ER stress condition is still unclear. Therefore, in order to explore the molecular mechanisms by which CLU inhibited ER stress-induced apoptosis, HCC cell lines were treated with tunicamycin (TN), an ER stress inducer. We found that the expressions of both CLU and GRP78 were increased after TN treatment. Knockdown of CLU expression in SMMC7721 and HCCLM3 cells inhibited GRP78 expression after TN treatment and enhanced ER stress-induced apoptosis, whereas over-expression of CLU in HepG2 cells increased GRP78 expression after TN induction and abolished the effect of TN on cell apoptosis. Furthermore, knockdown of GRP78 expression in CLU-HepG2 cells abrogated the protective role of CLU under ER stress condition. Co-immunoprecipitation (co-IP) and confocal microscopy experiments confirmed the direct interaction between CLU and GRP78 under ER stress condition. The effect of CLU knockdown on GRP78 expression and cell apoptosis in HCC tumors were further determined in orthotopic xenograft tumor model. Knockdown of CLU expression in HCCLM3 cells inhibited GRP78 expression in tumor tissues, accompanied with increased number of apoptotic cancer cells. Moreover, the correlation between CLU and GRP78 expression was further determined in clinical HCC specimens. Taken together, these findings reveal that CLU protects HCC cells from ER stress induced apoptosis at least partially through interacting with GRP78.
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