國家衛生研究院 NHRI:Item 3990099045/11961

NHRI > Institute of Biotechnology and Pharmaceutical Research > Ching-Chuan Kuo > Conference Papers/Meeting Abstract > Item 3990099045/11961

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11961

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:	[Ching-Chuan Kuo] Conference Papers/Meeting Abstract [Hsing-Pang Hsieh] Conference Papers/Meeting Abstract [Hsing-Jien Kung] Conference Papers/Meeting Abstract [Cheng-Chin Kuo] Conference Papers/Meeting Abstract

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