ArticleMolecular pharmacology2011
Copper transporter 2 regulates endocytosis and controls tumor growth and sensitivity to cisplatin in vivo.
Article in Molecular pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 67 citations in OpenAlex.
- Copper Homeostasis, Emerging Central Players in Cancer Immunotherapy.Journal of cellular and molecular medicine · 2025Review
- Mechanistic insights into cisplatin-induced ototoxicity: the central role of transient receptor potential channels.Frontiers in molecular biosciences · 2025Review
- Targeting ferroptosis as a potential strategy to overcome the resistance of cisplatin in oral squamous cell carcinoma.Frontiers in pharmacology · 2024Review
- Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.Mini reviews in medicinal chemistry · 2024Review
- Cancer Stem Cells in Renal Cell Carcinoma: Origins and Biomarkers.International journal of molecular sciences · 2023Review
- Review
- Mechanisms of Cisplatin Resistance in HPV Negative Head and Neck Squamous Cell Carcinomas.Cells · 2022Review
- Current Understanding of Membrane Transporters as Regulators or Targets for Cisplatin-Induced Hearing Loss.Molecular pharmacology · 2021Article
- Copper Sources for Sod1 Activation.Antioxidants (Basel, Switzerland) · 2020Review
- The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents.Frontiers in pharmacology · 2020Review
- Article
- Article
- Facilitating the Cellular Accumulation of Pt-Based Chemotherapeutic Drugs.International journal of molecular sciences · 2018Review
- Gene duplication and neo-functionalization in the evolutionary and functional divergence of the metazoan copper transporters Ctr1 and Ctr2.The Journal of biological chemistry · 2017Article
- Copper transporters and chaperones CTR1, CTR2, ATOX1, and CCS as determinants of cisplatin sensitivity.Metallomics : integrated biometal science · 2016Article
- NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells.Oncotarget · 2016Article
- Review
- EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer.PloS one · 2015Article
- The role of Ctr1 and Ctr2 in mammalian copper homeostasis and platinum-based chemotherapy.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2015Review
- Role of transporters in the distribution of platinum-based drugs.Frontiers in pharmacology · 2015Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Copper transporter 2 (CTR2) is one of the four copper transporters in mammalian cells that influence the cellular pharmacology of cisplatin and carboplatin. CTR2 was knocked down using a short hairpin RNA interference. Robust expression of CTR2 was observed in parental tumors grown in vivo, whereas no staining was found in the tumors formed from cells in which CTR2 had been knocked down. Knockdown of CTR2 reduced growth rate by 5.8-fold, increased the frequency of apoptotic cells, and decreased the vascular density, but it did not change copper content. Knockdown of CTR2 increased the tumor accumulation of cis-diamminedichloroplatinum(II) [cisplatin (cDDP)] by 9.1-fold and greatly increased its therapeutic efficacy. Because altered endocytosis has been implicated in cDDP resistance, uptake of dextran was used to quantify the rate of macropinocytosis. Knockdown of CTR2 increased dextran uptake 2.5-fold without reducing exocytosis. Inhibition of macropinocytosis with either amiloride or wortmannin blocked the increase in macropinocytosis mediated by CTR2 knockdown. Stimulation of macropinocytosis by platelet-derived growth factor coordinately increased dextran and cDDP uptake. Knockdown of CTR2 was associated with activation of the Rac1 and cdc42 GTPases that control macropinocytosis but not activation of the phosphoinositide-3 kinase pathway. We conclude that CTR2 is required for optimal tumor growth and that it is an unusually strong regulator of cisplatin accumulation and cytotoxicity. CTR2 regulates the transport of cDDP in part through control of the rate of macropinocytosis via activation of Rac1 and cdc42. Selective knockdown of CTR2 in tumors offers a strategy for enhancing the efficacy of cDDP.
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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.