Transcriptional adaptor 3 influences the proliferative and invasive phenotypes of non-small cell lung cancer cells via regulating EMT.

Abstract

Transcriptional adaptor 3 (TADA3/ADA3) is a conserved transcriptional co-activator and is dysregulated in many aggressive tumors. However, the role of TADA3 in non-small cell lung cancer (NSCLC) remains unknown. It was previously demonstrated that TADA3 expression correlates with poor prognosis in patients with NSCLC. In the present study, the expression and function of TADA3 were investigated in cells in vitro and in vivo. TADA3 expression was evaluated in clinical specimens and cell lines using reverse transcription-quantitative PCR and western blot analysis. The TADA3 protein level was significantly higher in human NSCLC specimens compared with matched normal tissues. In human NSCLC cell lines, short hairpin RNA-mediated silencing of TADA3 suppressed their proliferative, migratory and invasive abilities in vitro, and delayed G1 to S phase progression through the cell cycle. Consistent with this, TADA3 silencing increased expression of the epithelial marker E-cadherin and reduced expression of the mesenchymal markers, N-cadherin, Vimentin, Snail, and Slug. To verify the effect of TADA3 on tumor formation and growth in vivo, a mouse tumor xenograft model was established. TADA3 silencing slowed the growth of NSCLC tumor xenografts in nude mice, and excised tumors showed a similarly altered pattern of epithelial-mesenchymal transition (EMT) marker expression. The present results demonstrated the significance of TADA3 in regulating the growth and metastasis of NSCLC and may provide a theoretical basis for early diagnosis and targeted therapy of NSCLC.