title: Inhibition of EGFR-induced glucose metabolism sensitizes chondrosarcoma cells to cisplatin.
abstract: Chondrosarcomas are malignant cartilage-forming tumors which are resistant to conventional chemotherapy and radiotherapy. By searching in Oncomine which is a cancer microarray database and web-based data mining platform, we found Glut1 and LDHA were upregulated in human chondrosarcoma patient samples. In this study, we reported total epidermal growth factor receptor (EGFR) expression and phosphorylated EGFR were highly activated in human chondrosarcoma cell lines. In addition, overexpression of EGFR contributed to cisplatin resistance. EGFR promoted glucose metabolism of chondrosarcoma cells through the upregulation of glycolysis key enzymes. Interestingly, cisplatin-resistant chondrosarcoma cells showed upregulated glucose metabolism and EGFR signaling pathway. Finally, we demonstrated that the combination of either EGFR inhibitor or anaerobic glycolysis inhibitor with cisplatin showed synergistically inhibitory effects on cisplatin-resistant chondrosarcoma cells through the inducements of apoptosis and cell cycle arrest. Our project proposed a novel function of EGFR in the regulation of glucose metabolism in chondrosarcoma cells and contributed to the development of therapeutic strategies for the clinical treatment of chondrosarcoma patient.
authors.affiliation: Department of Orthopaedics, General Hospital of Daqing Oilfield, Daqing, 163001, China.
authors.forename: Yin-dong
authors.initials: YD
authors.lastname: Song
authors.forename: Ke-fei
authors.initials: KF
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Yan-qi
authors.initials: YQ
authors.lastname: Guo
authors.forename: Da-yong
authors.initials: DY
authors.lastname: Wang
authors.forename: Ming-yu
authors.initials: MY
authors.lastname: Cui
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Yuan-xin
authors.initials: YX
authors.lastname: Sun
authors.forename: Jian-hui
authors.initials: JH
authors.lastname: Shen
authors.forename: Xin-gang
authors.initials: XG
authors.lastname: Li
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.forename: Feng-jun
authors.initials: FJ
authors.lastname: Shi
mesh_terms: D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors; D005947:Glucose; D002945:Cisplatin
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