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Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway
Receptor tyrosine kinase (RTK) is activated by its natural ligand, mediating multiple essential biological processes. Copper (II) ions are bioactive ions and are crucial in the regulation of cell signaling pathway. However, the crosstalk between copper (II) ions and RTK-mediated cellular signaling r...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537018/ https://www.ncbi.nlm.nih.gov/pubmed/31218225 http://dx.doi.org/10.1155/2019/4158415 |
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author | He, Fang Chang, Cong Liu, Bowen Li, Zhu Li, Hao Cai, Na Wang, Hong-Hui |
author_facet | He, Fang Chang, Cong Liu, Bowen Li, Zhu Li, Hao Cai, Na Wang, Hong-Hui |
author_sort | He, Fang |
collection | PubMed |
description | Receptor tyrosine kinase (RTK) is activated by its natural ligand, mediating multiple essential biological processes. Copper (II) ions are bioactive ions and are crucial in the regulation of cell signaling pathway. However, the crosstalk between copper (II) ions and RTK-mediated cellular signaling remains unclear. Herein, we reported the effect of copper (II) ions on the ligand-independent RTK cellular signaling pathway. Our results indicate that both EGFR and MET signaling were activated by copper (II) in the absence of the corresponding ligands, EGF and HGF, respectively. Consequently, copper (II) ions initiate two RTK-mediated downstream signal transductions, including AKT and ERK. Moreover, copper (II) significantly increased proliferation and cellular migration. Our study proposes a novel role of copper in RTK-mediated signaling for growth factor-independent cancer cell proliferation and migration, implying that targeting both the copper (II) and growth factor in tumor microenvironments may be necessary for cancer treatment. |
format | Online Article Text |
id | pubmed-6537018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-65370182019-06-19 Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway He, Fang Chang, Cong Liu, Bowen Li, Zhu Li, Hao Cai, Na Wang, Hong-Hui Biomed Res Int Research Article Receptor tyrosine kinase (RTK) is activated by its natural ligand, mediating multiple essential biological processes. Copper (II) ions are bioactive ions and are crucial in the regulation of cell signaling pathway. However, the crosstalk between copper (II) ions and RTK-mediated cellular signaling remains unclear. Herein, we reported the effect of copper (II) ions on the ligand-independent RTK cellular signaling pathway. Our results indicate that both EGFR and MET signaling were activated by copper (II) in the absence of the corresponding ligands, EGF and HGF, respectively. Consequently, copper (II) ions initiate two RTK-mediated downstream signal transductions, including AKT and ERK. Moreover, copper (II) significantly increased proliferation and cellular migration. Our study proposes a novel role of copper in RTK-mediated signaling for growth factor-independent cancer cell proliferation and migration, implying that targeting both the copper (II) and growth factor in tumor microenvironments may be necessary for cancer treatment. Hindawi 2019-05-14 /pmc/articles/PMC6537018/ /pubmed/31218225 http://dx.doi.org/10.1155/2019/4158415 Text en Copyright © 2019 Fang He et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article He, Fang Chang, Cong Liu, Bowen Li, Zhu Li, Hao Cai, Na Wang, Hong-Hui Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway |
title | Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway |
title_full | Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway |
title_fullStr | Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway |
title_full_unstemmed | Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway |
title_short | Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway |
title_sort | copper (ii) ions activate ligand-independent receptor tyrosine kinase (rtk) signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537018/ https://www.ncbi.nlm.nih.gov/pubmed/31218225 http://dx.doi.org/10.1155/2019/4158415 |
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