TAB3 overexpression promotes cell proliferation in non-small cell lung cancer and mediates chemoresistance to CDDP in A549 cells via the NF-κB pathway.

Transforming growth factor-activated kinase 1 (TAK1)-binding protein 3 (TAB3) is essential for the activation of the nuclear factor kappa B (NF-κB) pathway and has important roles in cell survival. However, the contribution of TAB3 to non-small cell lung cancer (NSCLC) remains elusive. In the present study, Western blotting and immunohistochemistry assays demonstrated that TAB3 expression was frequently increased in NSCLC tissues and cells. In addition, chi-square test and Kaplan-Meier analysis revealed that upregulation of TAB3 expression correlated with a more invasive tumor phenotype and poor prognosis. In addition, a series of experiments, including serum starvation-refeeding experiment and TAB3-siRNA transfection assay, showed that TAB3 expression promoted NSCLC cell proliferation. Furthermore, the effect of TAB3 expression on the sensitivity to cis-diamminedichloroplatinum (CDDP) and possible signaling transduction pathways was investigated. When the expression of TAB3 was inhibited by siRNA transfection, the sensitivity to CDDP was enhanced. Moreover, it showed that downregulation of TAB3 enhanced CDDP-induced A549 cell apoptosis through the inhibition of the NF-κB pathway. These results suggest that TAB3 plays a critical role in NSCLC progression and chemoresistance and that TAB3 depletion may be a promising approach to lung cancer therapy.