Ge, Eva J, Bush, Ashley I, Casini, Angela, Cobine, Paul A, Cross, Justin R, DeNicola, Gina M, Dou, Q Ping, Franz, Katherine J, Gohil, Vishal M, Gupta, Sanjeev, Kaler, Stephen G, Lutsenko, Svetlana, Mittal, Vivek, Petris, Michael J, Polishchuk, Roman, Ralle, Martina, Schilsky, Michael L, Tonks, Nicholas K, Vahdat, Linda T, Van Aelst, Linda, Xi, Dan, Yuan, Peng, Brady, Donita C, Chang, Christopher J (November 2021) Connecting copper and cancer: from transition metal signalling to metalloplasia. Nature Reviews Cancer. ISSN 1474-175X
Abstract
Copper is an essential nutrient whose redox properties make it both beneficial and toxic to the cell. Recent progress in studying transition metal signalling has forged new links between researchers of different disciplines that can help translate basic research in the chemistry and biology of copper into clinical therapies and diagnostics to exploit copper-dependent disease vulnerabilities. This concept is particularly relevant in cancer, as tumour growth and metastasis have a heightened requirement for this metal nutrient. Indeed, the traditional view of copper as solely an active site metabolic cofactor has been challenged by emerging evidence that copper is also a dynamic signalling metal and metalloallosteric regulator, such as for copper-dependent phosphodiesterase 3B (PDE3B) in lipolysis, mitogen-activated protein kinase kinase 1 (MEK1) and MEK2 in cell growth and proliferation and the kinases ULK1 and ULK2 in autophagy. In this Perspective, we summarize our current understanding of the connection between copper and cancer and explore how challenges in the field could be addressed by using the framework of cuproplasia, which is defined as regulated copper-dependent cell proliferation and is a representative example of a broad range of metalloplasias. Cuproplasia is linked to a diverse array of cellular processes, including mitochondrial respiration, antioxidant defence, redox signalling, kinase signalling, autophagy and protein quality control. Identifying and characterizing new modes of copper-dependent signalling offers translational opportunities that leverage disease vulnerabilities to this metal nutrient.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > neoplasms diseases & disorders > cancer > drugs and therapies organs, tissues, organelles, cell types and functions Publication Type > review organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction organs, tissues, organelles, cell types and functions > tissues types and functions |
| CSHL Authors: | |
| Communities: | CSHL labs > Tonks lab CSHL labs > Van Aelst lab CSHL Cancer Center Program CSHL Cancer Center Program > Cellular Communication in Cancer Program |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 11 November 2021 |
| Date Deposited: | 17 Nov 2021 16:16 |
| Last Modified: | 09 Feb 2024 18:46 |
| PMCID: | PMC8810673 |
| URI: | https://repository.cshl.edu/id/eprint/40423 |
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