The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss

L. H. Tsai, J. Y. Wu, Y. W. Cheng, C. Y. Chen, G. T. Sheu, T. C. Wu, H. Lee

研究成果: 雜誌貢獻文章同行評審

40 引文 斯高帕斯(Scopus)

摘要

Liver kinase B1 (LKB1) loss in lung adenocarcinoma is commonly caused by genetic mutations, but these mutations rarely occur in Asian patients. We recently reported wild-type LKB1 loss via the alteration of NKX2-1/p53-axis-promoted tumor aggressiveness and predicted poor outcomes in cases of lung adenocarcinoma. The mechanistic action of wild-type LKB1 loss within tumor progression remains unknown. The suppression of MYC by LKB1 controls epithelial organization; therefore, we hypothesize that MYC expression can be increased via wild-type LKB1 loss and promotes tumor progression. Here, MYC transcription is upregulated by LKB1-loss-mediated MZF1 expression. The wild-type LKB1-loss-mediated MZF1/MYC axis is responsible for soft-agar growth, migration and invasion in lung adenocarcinoma cells. Moreover, wild-type LKB1 loss-induced cell invasiveness was markedly suppressed by MYC inhibitors (10058-F4 and JQ1). Patients with low-LKB1/high-MZF1 or low-LKB1/high-MYC tumors have shorter overall survival and relapse-free-survival periods than patients with high-LKB1/low-MZF1 or high-LKB1/low-MYC tumors. In summary, MZF1-mediated MYC expression may promote tumor progression, resulting in poor outcomes in cases of lung adenocarcinoma with low-wild-type-LKB1 tumors.
原文英語
頁(從 - 到)1641-1649
頁數9
期刊Oncogene
34
發行號13
DOIs
出版狀態已發佈 - 三月 26 2015

ASJC Scopus subject areas

  • Medicine(all)

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