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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Copper (II) Ions Activate Ligand-Independent Receptor Tyrosine Kinase (RTK) Signaling Pathway
Fang He1, Cong Chang1, Bowen Liu1
1Institute of Nanotechnology and Tissue Engineering, College of Biology, Hunan University, Changsha, 410082, China.
Abstract:
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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