ASCT2 (SLC1A5) is an EGFR-associated protein that can be co-targeted by cetuximab to sensitize cancer cells to ROS-induced apoptosis

Highlights • ASCT2 is physically associated with EGFR in a molecular complex. • Cetuximab downregulates ASCT2 via cetuximab-mediated EGFR endocytosis. • Co-targeting ASCT2 by cetuximab sensitizes HNSCC cells to ROS-induced apoptosis. • Cetuximab sensitizes ROS-induced apoptosis independent of EGFR k...

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Veröffentlicht in:	Cancer letters 2016-10, Vol.381 (1), p.23-30
Hauptverfasser:	Lu, Haiquan, Li, Xinqun, Lu, Yang, Qiu, Songbo, Fan, Zhen
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Transport System ASC - metabolism Antineoplastic Agents - pharmacology Antineoplastic Combined Chemotherapy Protocols - pharmacology Apoptosis Apoptosis - drug effects ASCT2 Cancer Cancer therapies Carcinoma, Squamous Cell - drug therapy Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell Line, Tumor Cetuximab Cetuximab - pharmacology Clinical trials Dichloroacetic Acid - pharmacology Down-Regulation EGFR Endocytosis - drug effects ErbB Receptors - antagonists & inhibitors ErbB Receptors - genetics ErbB Receptors - metabolism Gefitinib Glutamine - metabolism Glutathione Glutathione - metabolism Head and Neck Neoplasms - drug therapy Head and Neck Neoplasms - genetics Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - pathology Hematology, Oncology and Palliative Medicine HNSCC Humans Hypotheses Immunoglobulins Kinases Metabolic disorders Metastasis Minor Histocompatibility Antigens - metabolism Oxidative Stress - drug effects Phosphorylation Protein Kinase Inhibitors - pharmacology Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Proteins Quinazolines - pharmacology Radiation therapy Reactive Oxygen Species - metabolism RNA Interference ROS Signal Transduction - drug effects Squamous Cell Carcinoma of Head and Neck Studies Time Factors Transfection Tumors
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Zusammenfassung:	Highlights • ASCT2 is physically associated with EGFR in a molecular complex. • Cetuximab downregulates ASCT2 via cetuximab-mediated EGFR endocytosis. • Co-targeting ASCT2 by cetuximab sensitizes HNSCC cells to ROS-induced apoptosis. • Cetuximab sensitizes ROS-induced apoptosis independent of EGFR kinase inhibition.
ISSN:	0304-3835 1872-7980
DOI:	10.1016/j.canlet.2016.07.020