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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...

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Detalles Bibliográficos
Autores principales: He, Fang, Chang, Cong, Liu, Bowen, Li, Zhu, Li, Hao, Cai, Na, Wang, Hong-Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
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.
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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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