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Inhibition of EGFR-induced glucose metabolism sensitizes chondrosarcoma cells to cisplatin

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Tumor Biology

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.

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Authors and Affiliations

  1. Department of Orthopaedics, General Hospital of Daqing Oilfield, Daqing, 163001, China

    Yin-dong Song, Ke-fei Zhang, Dong Liu, Da-yong Wang, Ming-yu Cui, Gang Li, Yuan-xin Sun, Jian-hui Shen, Xin-gang Li, Long Zhang & Feng-jun Shi

  2. Department of Emergency Surgery, General Hospital of Daqing Oilfied, Daqing, 163001, China

    Yan-qi Guo

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  1. Yin-dong Song
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  2. Ke-fei Zhang
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  3. Dong Liu
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  5. Da-yong Wang
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  7. Gang Li
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  11. Long Zhang
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  12. Feng-jun Shi
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Correspondence to Feng-jun Shi.

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Song, Yd., Zhang, Kf., Liu, D. et al. Inhibition of EGFR-induced glucose metabolism sensitizes chondrosarcoma cells to cisplatin. Tumor Biol. 35, 7017–7024 (2014). https://doi.org/10.1007/s13277-014-1902-4

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  • DOI: https://doi.org/10.1007/s13277-014-1902-4

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