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http://ir.nhri.org.tw/handle/3990099045/11961
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| Title: | Blockage of EGFR signaling repurposes tumor metabolism through suppression of glycolysis and Kreb cycle in head and neck cancer |
| Authors: | Kuo, CC;Chang, JY;Hsieh, HP;Kung, HJ;Chang, HH;Huang, CH;Kuo, CC;Ke, YY |
| Contributors: | Institute of Biotechnology and Pharmaceutical Research;Institute of Molecular and Genomic Medicine;Institute of Cellular and Systems Medicine |
| Abstract: | Head and neck squamous cell carcinoma (HNSCC), the most common malignant neoplasm arising in the mucosa of the upper aerodigestive tract, remains a significant cause of morbidity worldwide. With respect to the cancer treatment, HNSCC has a moderately good survival rate, however, the disease often recurs, leading to a poor prognostic disease course and tends to fail in treatment. The metabolic properties of cancer cells diverge significantly from those of normal cells. Emerging evidence suggests these metabolic alterations are also linked to therapeutic resistance in cancer treatment. EGFR targeted agents currently approved or under investigation for HNSCC. We recently identified a novel EGFR tyrosine kinase inhibitor (EGFR-TKI), BPR3K007S0, and found that this compound significantly inhibited EGFR phosphorylation in EGFR-overexpressing HNSCC cells in vitro and in vivo than that of gefitinib. BPR3K007S0 significantly suppressed the expression of a wide range of metabolic genes, including metabolic-related transcription factors, glycolysis, TCA cycle, and pentose phosphate pathway genes. Collectively, we also found that BPR3K007S0 significantly decreased glycolytic and mitochondria respiratory capacity. Pharmacological and genetic manipulation demonstrated that c-Myc/hexokinase 2 axis was one of downstream effector in response to EGFR inhibition. Furthermore, we found that EGFR-TKIs were able to suppress succinate dehydrogenase A leading to reduce fumarate, an oncometabolite generates from Kreb cycle, and contributed to EGFR-TKIs mediated antitumor effect. Taken together, these results revealed that blockage of EGFR signaling repurposes tumor metabolism through suppression of hexokinase 2 and succinate dehydrogenase A, in glycolysis and Kreb cycle, respectively, and demonstrated added benefits to treatment of HNSCCs. |
| Date: | 2018-07 |
| Relation: | Cancer Research. 2018 Jul;78(13, Suppl.):Meeting Abstract 3944. |
| Link to: | http://dx.doi.org/10.1158/1538-7445.Am2018-3944 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000468819502199 |
| Appears in Collections: | [郭靜娟] 會議論文/會議摘要
[謝興邦] 會議論文/會議摘要
[龔行健] 會議論文/會議摘要
[郭呈欽] 會議論文/會議摘要
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