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

Affiliation

Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA; Developmental Therapeutics and Cell Biology Programs, Cancer Center, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: [Email]

Abstract

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 (LUAD) 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.

Keywords

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