期刊
JOURNAL OF DRUG TARGETING
卷 27, 期 4, 页码 460-465出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/1061186X.2018.1550648
关键词
Lung adenocarcinoma; PDK2; CNNM3; cisplatin-resistance
资金
- National Natural Science Foundation of China [81501987]
- Natural Science Basic Research Plan in Shaanxi Province of China [2015JQ8314]
- Fundamental Research Funds for the Central Universities [1191320095]
Recurrence of lung adenocarcinoma has become one of the most frequent causes of major cancer incidence and mortality worldwide according to its frequently gained resistance to chemotherapies. In this study, we identified a poorly-studied kinase pyruvate dehydrogenase kinase isoform 2 (PDK2) as the most up-regulated kinase encoding gene in Cisplatin resistant lung adenocarcinoma. Additionally, PDK2-dependent Cisplatin-resistance promotes tumour growth of lung adenocarcinoma both in vitro and in vivo. Clinically, PDK2 expression was up-regulated in lung adenocarcinoma and was correlated to the poor prognosis of lung cancer patients. Mechanically, PDK2 promoted cell growth and Cisplatin-resistance of lung adenocarcinoma via transcriptional regulation of cyclin and CBS domain divalent metal cation transport mediator 3 (CNNM3), indicating that PDK2-CNNM3 signalling axis could be a potential therapeutic target for Cisplatin-resistant lung adenocarcinoma.
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