https://scholars.lib.ntu.edu.tw/handle/123456789/557699
標題: | Lysine deprivation induces AKT-AADAT signaling and overcomes EGFR-TKIs resistance in EGFR-mutant non-small cell lung cancer cells | 作者: | Hsu C.-C. Yang A.Y.-P. Chen J.-Y. Tsai H.-H. Lin S.-H. Tai P.-C. Huang M.-H. Hsu W.-H. Lin A.M.-Y. CHIH-HSIN YANG |
關鍵字: | AADAT; EGFR-mutant NSCLC; EGFR-TKI resistance; Lysine deprivation; Osimertinib | 公開日期: | 2021 | 出版社: | MDPI AG | 卷: | 13 | 期: | 2 | 起(迄)頁: | 1��17�� | 來源出版物: | Cancers | 摘要: | Epidermal growth factor receptor (EGFR) mutations are the most common driver genes in non-small cell lung cancer (NSCLC), especially in the Asian population. Although EGFR-tyrosine kinase inhibitors (TKIs) are influential in the treatment of EGFR-mutant NSCLC patients, acquired resistance inevitably occurs. Therefore, there is an urgent need to develop strategies to overcome this resistance. In addition, cancer cells with particular mutations appear more vulnerable to deficiency related to the availability of specific amino acids. However, it is still unknown which amino acid is affected in the case of EGFR-mutant NSCLC. In the present study, we established a screening platform based on amino acid deprivation and found that EGFR-mutant NSCLC cells are sensitive to short-term lysine deprivation. Moreover, we found that expression of the gene for the lysine catabolism enzyme α-aminoadipate aminotransferase (AADAT) increased under lysine deprivation, revealing that AADAT can be regulated by EGFR-AKT signaling. Finally, we found that lysine reduction can not only enhance the cytostatic effect of single-agent osimertinib but also overcome the resistance of EGFR-TKIs in EGFR-mutant NSCLC cells. In summary, our findings suggest that the introduction of lysine stress might act as an advancement in EGFR-mutant NSCLC therapy and offer a strategy to overcome EGFR-TKI resistance. ? 2021 by the authors. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099578959&doi=10.3390%2fcancers13020272&partnerID=40&md5=2fb508affde01316daabc731a5528b76 https://scholars.lib.ntu.edu.tw/handle/123456789/557699 |
ISSN: | 2072-6694 | DOI: | 10.3390/cancers13020272 | SDG/關鍵字: | 2 aminoadipate aminotransferase; 8 [4 (1 aminocyclobutyl)phenyl] 9 phenyl 1,2,4 triazolo[3,4 f][1,6]naphthyridin 3(2h) one; afatinib; epidermal growth factor receptor; gefitinib; lysine; osimertinib; protein kinase B; AADAT gene; animal cell; Article; catabolism; cell survival; controlled study; cytostasis; EGFR gene; gene expression; gene function; gene mutation; HCC4006 cell line; HCC827 cell line; human; human cell; lung non-small cell carcinoma cell line; nonhuman; oncogene; rat; signal transduction |
顯示於: | 腫瘤醫學研究所 |
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