4.6 Article

Nuclear TAZ activity distinctly associates with subtypes of non-small cell lung cancer

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.01.012

Keywords

TAZ; Nuclear localization; Non-small cell lung cancer; Subtype; Outcome

Funding

  1. Mayo Clinic NIH relief program [CA218109relief]
  2. center for biomedical discovery platform award
  3. National Natural Science Foundation of China [81370174, 81673014, 81372347]
  4. Outstanding Academic Leaders Plan of Shanghai Municipal Science and Technology Committee [16XD1403100]
  5. National Key RD Plan [2017YFA0104600]

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The transcription co-factor TAZ plays critical roles in the regulation of human carcinogenesis. However, the pathological role for TAZ in lung cancer has remained incompletely understood. TAZ expression was examined by immunohistochemistry for 163 NSCLC tissues. TAZ expression was also examined by western blotting for 20 frozen paired NSCLC and adjacent normal lung tissues. We report that TAZ is overexpressed in non-small cell lung cancer (NSCLC) tissues and correlates with shorter patient survival. Intriguingly, we find that TAZ is overexpressed primarily in lung squamous cell carcinomas (LUSC) but not lung adenocarcinomas (WAD) compared to normal lung tissues, and that the expression levels of TAZ are significantly higher in LUSC than LUAD. The nuclear localization of TAZ correlates worse clinical outcomes in LUSC, but not LUAD, further suggesting a prognostic value for activated TAZ in LUSC. A meta analysis of the public datasets from TCGA, Broad institute, and Oncomine shows that the TAZ gene (WWTR1) copy numbers are significantly increased in LUSC and correlate with the increase of TAZ mRNA expression, suggesting that TAZ is overexpressed in LUSC at least partly through gene amplifications. Collectively, our results suggest that TAZ expression distinctly associates with subtypes of NSCLC and may be useful for developing novel therapeutics treating LUSC. (C) 2019 Elsevier Inc. All rights reserved.

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