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

Research output: Contribution to journalArticle

31 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

Fingerprint

Phosphotransferases
Liver
Neoplasms
Adenocarcinoma of lung
Mutation
Survival
Agar
Organizations
Recurrence
Growth

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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

The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss. / Tsai, L. H.; Wu, J. Y.; Cheng, Y. W.; Chen, C. Y.; Sheu, G. T.; Wu, T. C.; Lee, H.

In: Oncogene, Vol. 34, No. 13, 26.03.2015, p. 1641-1649.

Research output: Contribution to journalArticle

Tsai, LH, Wu, JY, Cheng, YW, Chen, CY, Sheu, GT, Wu, TC & Lee, H 2015, 'The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss', Oncogene, vol. 34, no. 13, pp. 1641-1649. https://doi.org/10.1038/onc.2014.118
Tsai LH, Wu JY, Cheng YW, Chen CY, Sheu GT, Wu TC et al. The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss. Oncogene. 2015 Mar 26;34(13):1641-1649. https://doi.org/10.1038/onc.2014.118
Tsai, L. H. ; Wu, J. Y. ; Cheng, Y. W. ; Chen, C. Y. ; Sheu, G. T. ; Wu, T. C. ; Lee, H. / The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss. In: Oncogene. 2015 ; Vol. 34, No. 13. pp. 1641-1649.
@article{1f1620bf6ae545d69f0cb6c5b2742927,
title = "The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss",
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.",
author = "Tsai, {L. H.} and Wu, {J. Y.} and Cheng, {Y. W.} and Chen, {C. Y.} and Sheu, {G. T.} and Wu, {T. C.} and H. Lee",
year = "2015",
month = "3",
day = "26",
doi = "10.1038/onc.2014.118",
language = "English",
volume = "34",
pages = "1641--1649",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "13",

}

TY - JOUR

T1 - The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss

AU - Tsai, L. H.

AU - Wu, J. Y.

AU - Cheng, Y. W.

AU - Chen, C. Y.

AU - Sheu, G. T.

AU - Wu, T. C.

AU - Lee, H.

PY - 2015/3/26

Y1 - 2015/3/26

N2 - 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.

AB - 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.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-84899589163&origin=resultslist&sort=plf-f&src=s&sid=b7ce84567057405a7e4592d942ee3341&sot=a&sdt=a&sl=17&s=AU-ID%287404915168%29&relpos=24&citeCnt=22&searchTerm=

UR - https://www.scopus.com/results/citedbyresults.uri?sort=plf-f&cite=2-s2.0-84899589163&src=s&imp=t&sid=b6c041bac4e806ddb077d2c0dc4363ff&sot=cite&sdt=a&sl=0&origin=recordpage&editSaveSearch=&txGid=902341e077f010d15bbde5e94145963d

U2 - 10.1038/onc.2014.118

DO - 10.1038/onc.2014.118

M3 - Article

VL - 34

SP - 1641

EP - 1649

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 13

ER -