ArticleBMC cancer2008
Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells.
Article in BMC cancer, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 122 citations in OpenAlex.
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- Nanocarrier-based delivery of Pt(IV) compounds for chemoimmunotherapy and theranostics: Advances, challenges, and prospects.Acta pharmaceutica Sinica. B · 2026Review
- Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).Cell communication and signaling : CCS · 2026Review
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Article
- GPT2 mediates glutamine metabolism-driven metabolic alterations in platinum-resistant ovarian cancer cells.Scientific reports · 2025Article
- Epidrug screening identifies type I PRMT inhibitors as modulators of lysosomal exocytosis and drug sensitivity in cancers.Cell death & disease · 2025Article
- Cuproptosis inhibits tumor progression and enhances cisplatin toxicity in ovarian cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer.Molecular biomedicine · 2025Review
- Recent Advances in Anticancer Research of Osmium and Rhodium Complexes.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- SPG21, a potential oncogene targeted by miR-128-3p, amplifies HBx-induced carcinogenesis and chemoresistance via activation of TRPM7-mediated JNK pathway in hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Analysis of ATP7A Expression and Ceruloplasmin Levels as Biomarkers in Patients Undergoing Neoadjuvant Chemotherapy for Advanced High-Grade Serous Ovarian Carcinoma.International journal of molecular sciences · 2024Article
- Cuproptosis in cancer: biological implications and therapeutic opportunities.Cellular & molecular biology letters · 2024Review
- Chemo-small extracellular vesicles released in cisplatin-resistance ovarian cancer cells are regulated by the lysosomal function.Journal of extracellular biology · 2024Article
- Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.Mini reviews in medicinal chemistry · 2024Review
- The Antineoplastic Effect of Carboplatin Is Potentiated by Combination with Pitavastatin or Metformin in a Chemoresistant High-Grade Serous Carcinoma Cell Line.International journal of molecular sciences · 2022Article
- Addition of Gallic Acid Overcomes Resistance to Cisplatin in Ovarian Cancer Cell Lines.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Can Cisplatin Therapy Be Improved? Pathways That Can Be Targeted.International journal of molecular sciences · 2022Review
- Lysosomal inhibition sensitizes TMEM16A-expressing cancer cells to chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Ion Channel Involvement in Tumor Drug Resistance.Journal of personalized medicine · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCopper homeostasis proteins ATP7A and ATP7B are assumed to be involved in the intracellular transport of cisplatin. The aim of the present study was to assess the relevance of sub cellular localisation of these transporters for acquired cisplatin resistance in vitro. For this purpose, localisation of ATP7A and ATP7B in A2780 human ovarian carcinoma cells and their cisplatin-resistant variant, A2780cis, was investigated.
methodsSub cellular localisation of ATP7A and ATP7B in sensitive and resistant cells was investigated using confocal fluorescence microscopy after immunohistochemical staining. Co-localisation experiments with a cisplatin analogue modified with a carboxyfluorescein-diacetate residue were performed. Cytotoxicity of the fluorescent cisplatin analogue in A2780 and A2780cis cells was determined using an MTT-based assay. The significance of differences was analysed using Student's t test or Mann-Whitney test as appropriate, p values of < 0.05 were considered significant.
resultsIn the sensitive cells, both transporters are mainly localised in the trans-Golgi network, whereas they are sequestrated in more peripherally located vesicles in the resistant cells. Altered localisation of ATP7A and ATP7B in A2780cis cells is likely to be a consequence of major abnormalities in intracellular protein trafficking related to a reduced lysosomal compartment in this cell line. Changes in sub cellular localisation of ATP7A and ATP7B may facilitate sequestration of cisplatin in the vesicular structures of A2780cis cells, which may prevent drug binding to genomic DNA and thereby contribute to cisplatin resistance.
conclusionOur results indicate that alterations in sub cellular localisation of transport proteins may contribute to cisplatin resistance in vitro. Investigation of intracellular protein localisation in primary tumour cell cultures and tumour tissues may help to develop markers of clinically relevant cisplatin resistance. Detection of resistant tumours in patients may in turn enable individualization of the chemotherapy in the early stage of treatment.
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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.