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

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35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1641-1649
Number of pages9
JournalOncogene
Volume34
Issue number13
DOIs
Publication statusPublished - Mar 26 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Tsai, L. H., Wu, J. Y., Cheng, Y. W., Chen, C. Y., Sheu, G. T., Wu, T. C., & Lee, H. (2015). The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss. Oncogene, 34(13), 1641-1649. https://doi.org/10.1038/onc.2014.118