Chimeric ubiquitin ligases inhibit non-small cell lung cancer via negative modulation of EGFR signaling

Highlights • We generated two chimeric ubiquitin ligases SH2-RING and SH2-U-box. • The chimeric ligases can bind EGFR and enhance its ubiquitination and degradation. • These ligases down-regulate EGFR and attenuate EGFR signaling in SPC-A1 cells. • These ligases inhibit the malignancy of SPC-A1 cell...

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Veröffentlicht in:	Cancer letters 2015-04, Vol.359 (1), p.57-64
Hauptverfasser:	Zhong, Daixing, Ru, Yi, Wang, Qinhao, Zhang, Jing, Zhang, Jian, Wei, Junxia, Wu, Jin, Yao, Libo, Li, Xiaofei, Li, Xia
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antibiotics, Antineoplastic - pharmacology Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology Antineoplastic Combined Chemotherapy Protocols - pharmacology Apoptosis - drug effects Binding Sites Cancer therapies Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - enzymology Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology Catalytic Domain Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Doxorubicin - pharmacology EGFR Enzymes Genes Hematology, Oncology and Palliative Medicine Humans Kinases Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - enzymology Lung Neoplasms - pathology Mice, Nude Mutation Nanoparticles Neoplasm Invasiveness NSCLC Phosphatidylinositol 3-Kinase - metabolism Plasmids Protein Interaction Domains and Motifs Proteins Proteolysis Proto-Oncogene Proteins c-akt - metabolism Receptor, Epidermal Growth Factor - metabolism Recombinant Fusion Proteins - pharmacology Signal Transduction - drug effects Software src Homology Domains Targeted therapy Time Factors Transfection Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism Ubiquitin-Protein Ligases - pharmacology Ubiquitination
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Zusammenfassung:	Highlights • We generated two chimeric ubiquitin ligases SH2-RING and SH2-U-box. • The chimeric ligases can bind EGFR and enhance its ubiquitination and degradation. • These ligases down-regulate EGFR and attenuate EGFR signaling in SPC-A1 cells. • These ligases inhibit the malignancy of SPC-A1 cells in vitro and in vivo. • EGFR-targeting chimeric ligases may be applied to targeted therapy for NSCLC.
ISSN:	0304-3835 1872-7980
DOI:	10.1016/j.canlet.2014.12.043